Tris-hydroxymethyl alkane esters as low calorie fat mimetics

Trishydroxymethyl alkanes, notably monomeric and dimeric trishydroxymethyl ethane and propane, esterified with fatty acids or dicarboxylate-extended fatty acid derivatives, are physiologically compatible, partially digestible edible synthetic fat replacements for foods and pharmaceuticals.

BACKGROUND OF THE INVENTION 
This invention relates to the use of monomeric and dimeric 
trishydroxymethyl alkane fatty acid esters and fatty acid ester 
derivatives as partially digestible edible synthetic fat replacements in 
food and pharmaceuticals. 
Since fats provide nine calories per gram compared to four calories per 
gram provided by protein or carbohydrates, major research efforts toward 
reduction of caloric intake for medical or health reasons have focused on 
ways to produce food substances that provide the same functional and 
organoleptic properties as fats, but not the calories. 
A major strategy for developing low calorie replacement fats has been to 
structurally re-engineer natural triglycerides in such a way as to retain 
their conventional functional properties in foods, while removing their 
susceptibility toward hydrolysis or subsequent absorption during 
digestion. To this end, the fatty acids attached to glycerol have been 
replaced with alternate acids (U.S. Pat. No. 3,579,548 to Whyte); groups 
have been inserted between the fatty acids and the glycerol backbone 
("propoxylated glycerols", Eur. Pat. Ap. No. 254,547 to White and 
Pollard); the ester linkages have been replaced by ether linkages (U.S. 
Pat. No. 3,818,089 to Bayley and Carlson, and Can. Pat. No. 1,106,681 to 
Trost); the ester linkages have been reversed (U.S. Pat. No. 4,508,746 to 
Hamm); and the glycerol moiety has been replaced with an alternate alcohol 
(e.g., ethylene glycol in U.S. Pat. No. 2,924,528 to Barskey et al., and 
U.S. 2,993,063 to Alsop and Carr). 
A second major approach to the development of a low calorie fat replacement 
has been to explore or synthesize nonabsorbable polymeric materials 
structurally unlike triglycerides, but having physical properties similar 
to edible fat. Mineral oil was disclosed as early as 1894 (U.S. Pat. No. 
519,980 to Winter), and, more recently, polydextrose (U.S. Pat. No. 
4,631,196 to Zeller), polyglucose and polymaltose (U.S. Pat. No. 3,876,794 
to Rennhard), polysiloxane (Eur. Pat. Ap. No. 205,273 to Frye), jojoba wax 
(W. Ger. Pat. No. 3,529,564 to Anika), and polyethylene polymers (E. Ger. 
Pat. No. 207,070 to Mieth, et al.) have been suggested. 
A third major strategy combines the first two. Rather than restructure 
triglyceride molecules or find a substitute structurally very dissimilar, 
this approach explores the use of various polyol esters, compounds which 
have numbers of fatty acid groups in excess of the three in conventional 
fat triglycerides, as nonabsorbable fat replacements. Fully esterified 
sugars were suggested as fat replacements during World War I (notably 
mannitol, Lapworth, A., and Pearson, L. K., and Halliburton, W. D., et 
al., 13 J. Biol. Chem. 296 and 301 (1919)), and the Southern and Western 
Regional Research Laboratories of the U.S.D.A. investigated the 
feasibility of using amylose esters as new-type fats during the 1960's 
(see Booth, A. N., and Gros, A. T., 40 J. Amer. Oil Chem. Soc. 551 (1963) 
and the references cited therein). More recently, sucrose polyesters have 
been suggested (U.S. Pat. No. 3,600,186 to Mattson and Volpenhein). The 
caloric availability and digestibility of a series of dimeric and 
polymeric glycerides including diglyceride esters of succinic, fumaric, 
and adipic acids, and polymeric fats from stearic, oleic and short-chain 
dibasic acids were assessed by the U.S.D.A. group cited supra, and 
polyglycerol esters have since been suggested (U.S. Pat. No. 3,637,774 to 
Babayan and Lehman). 
Nondigestible or nonabsorbable triglyceride analogues, polyol esters, and 
polymeric materials have proved disappointing as fat replacements when 
tested in feeding trials, where gastrointestinal side effects occurred, in 
some cases so extreme that frank anal leakage was observed (for recent 
reviews, see Hamm, D. J., 49 J. Food Sci. 419 (1984) and Haumann, B. J., 
63 J. Amer. Oil Chem. Soc. 278 (1986)). Nondigestible fats act as a 
laxative and are expelled from the body, eliciting foreign body reactions 
like those early documented for mineral oil (Goodman and Gilman's 
Pharmacological Basis of Therapeutics, 7th ed., Macmillan Pub. Co., N.Y. 
1985, pp. 1002-1003). Polyglycerol and polyglycerol esters, for example, 
suggested as fat replacements supra, have been suggested for use as fecal 
softening agents as well (U.S. Pat. No. 3,495,010 to Fossel). A number of 
remedies have been recommended to combat the anal leakage observed when 
sucrose polyesters are ingested (e.g., employing cocoa butters, U.S. Pat. 
No. 4,005,195 to Jandacek, or incorporating saturated fatty groups, Eur. 
Pat. Ap. No. 233,856 to Bernhardt), and dietary fiber preparations have 
been incorporated into polysaccharide and/or polyol-containing foodstuffs 
to help inhibit the diarrheal effect (U.S. Pat. No. 4,304,768 to Staub et 
al.). 
SUMMARY OF THE INVENTION 
An object of the present invention is to provide a fat replacement more 
compatible with normal digestion. More particularly, it is an object of 
the present invention to provide a more digestible fat replacement which 
interferes less with fat metabolism, thus avoiding diarrhea and other 
laxative side effects. It is a further object of the present invention to 
provide a partially digestible fat replacement which may, if desired, be 
engineered to provide essential fatty acids. 
In the practice of this invention, trishydroxymethyl alkane ester 
derivatives, notably fatty acid and dicarboxylate-extended fatty acid 
esters of monomeric and dimeric trishydroxymethyl alkanes, are partially 
digestible edible fat replacements. These fat replacements are more 
physiologically compatible than the nondigestible replacements heretofore 
developed. 
DETAILED DESCRIPTION OF THE INVENTION 
Minich suggested neopentyl alcohol esters as fat substitutes in dietetic 
compositions (U.S. Pat. No. 2,962,419). He used pentaerythritol, a 
tetrahydric neopentyl sugar alcohol formed when pentaerythrose condensed 
from acetaldehyde and formaldehyde undergoes a crossed Cannizzaro 
reaction, in his examples He tested pentaerythritol tetracaprylate in 
lipase assays and found the "esters are not attacked, hydrolyzed, by the 
enzyme pancreatic lipase, and therefore, cannot be assimilated" (col. 4, 
lines 62-64). In a feeding study using the same compound, rats fed 
pentaerythritol tetracaprylate ad libitum consumed more than control 
animals on a normal diet. "If the rats on the fat-free diet had been 
limited to the same amount of food, their weight would have been less" 
(col. 5, lines 49-51). He concluded that the esters, which "do not break 
down in the stomach or upper intestinal tract . . . may be used to control 
the intake of fat" (col. 1, lines 63-65). 
Long known to be useful as high temperature lubricants (see reviews by 
Barnes, R. S., and Fainman, M. Z., 13 Lub. Eng. 454 (1957), and Bell, E. 
W., et al., 53 J. Amer. Oil Chem. Soc. 511 (1976)), the family of 
compounds have since been often cited in patents and periodicals as 
examples of nondigestible triglyceride analogues which sterically hinder 
normal fat hydrolysis because of branching on the alcohol side of the 
triglyceride molecule. 
The present invention is based on the surprising finding that 
tris-hydroxymethyl alkane esters, which have three side chains rather than 
the four of Minich's pentaerythritol esters, are not nondigestible. On the 
contrary, trishydroxymethyl alkane esters are partially digestible. Slowly 
hydrolyzed by lipase in vitro, the esters exhibit, in in vivo feeding 
studies, a caloric availability qualitatively a fraction that of natural 
fat. Instead of passing through the digestive tract unchanged, eliciting 
the undesirable side effects of oral foreign nondigestible materials 
discussed above, the tris-hydroxymethyl alkane esters are a food. 
The present invention is also based on the finding that trishydroxymethyl 
alkane esters esterified with dicarboxylic acid-extended fatty acid 
derivatives not suggested by Minich, supra, exhibit desirable properties 
as edible fat mimetics. And dimeric trishydroxymethyl alkanes are similar 
to their monomeric counterparts. Together, monomeric and dimeric 
trishydroxymethyl alkane fatty acid and dicarboxylic acid-extended fatty 
acid esters comprise a new class of partially digestible synthetic fat 
mimetics. 
The trishydroxymethyl alkane esters of this invention comprise esterified 
trishydroxymethyl compounds having the following general formula: 
##STR1## 
where 
n=1 or 2, 
X is an alkyl group having from 1 to 5 carbons when n=1, or an alkyl, ether 
or ester bridge having 1 to 8 carbons when n=2, and 
F.sub.1, F.sub.2, and F.sub.3 are fatty acid residues or 
dicarboxylate-extended fatty acid residues. 
Thus, the compounds of this invention comprise monomeric trishydroxymethyl 
alkane esters of the general formula 
##STR2## 
or a trishydroxymethyl alkane ester dimer coupled by an alkyl, ether, or 
ester bridge having 1 to 8 carbons of the general formula: 
##STR3## 
where 
R is an alkyl group having from 1 to 5 carbons, 
X is an alkyl, ether or ester bridge having 1 to 8 carbons, and 
F.sub.1, F.sub.2, and F.sub.3 are fatty acid residues or 
dicarboxylate-extended fatty acid residues. 
In the monomeric esters, group R attached to the central carbon, C, may be 
linear or branched, saturated or unsaturated. Thus, this invention 
comprises compounds having a neopentyl nucleus, C, to which are attached, 
in ester linkage to hydroxymethyl groups, --CH.sub.2 --O--, three fatty 
acid or dicarboxylate-extended fatty acid residues F.sub.1, F.sub.2, and 
F.sub.3, and one aliphatic group R, e.g., methyl or ethyl 
In the dimeric esters, the R group may be replaced by a bridge X between 
two neopentyl nuclei of similar structure. The bridge X can be an alkyl 
bridge of the general formula, 
EQU (--CH.sub.2 --).sub.n, 
an ether bridge of the general formula, 
EQU --CH.sub.2 --O--CH.sub.2 -- or --CH.sub.2 --O--(CH.sub.2).sub.n 
--O--CH.sub.2 --, 
or an ester bridge of the general formula, 
EQU --CH.sub.2 --O--(CO)--(CH.sub.2).sub.n --(CO)--O--CH.sub.2 --, 
where n=1 to 4. Bridge X can have a total of from one to eight carbons; in 
the formulae above, where X is an alkyl and n=1, X has one carbon, and 
where X is an ester and n=4, X has eight carbons. One preferred dimeric 
compound is linked by the ether bridge --CH.sub.2 --O--CH.sub.2 --, formed 
by the condensation of two trishydroxymethyl alkane alcohols prior to 
esterification. Another preferred dimeric compound is linked by the ester 
bridge --CH.sub.2 --O--(CO)--(CH.sub.2).sub.n --(CO)--O--CH.sub.2, where 
n=1 or 2, formed by the condensation of two trishydroxymethyl alkane 
alcohols with one molecule of malonic (HOOC--CH.sub.2 --COOH) or succinic 
acid (HOOC--(CH.sub.2).sub.2 --COOH) prior to esterification. 
Thus, the compounds of this invention comprise trishydroxymethyl monomeric 
or dimeric alcohols fully esterified with fatty acids or 
dicarboxylate-extended fatty acids to form physiologically compatible fat 
replacements for foods and pharmaceuticals. 
Examples of trishydroxymethyl alcohols forming the compound backbones are 
trishydroxymethyl ethane, trishydroxymethyl propane, trishydroxymethyl 
butane, and trishydroxymethyl pentane, and their dimers. Chemical 
descriptions and formulae used here include isomeric variations. 
The fatty acid residues, F.sub.1, F.sub.2, and F.sub.3, may be the same or 
different, and may comprise a mixture of residues The term "fatty acids" 
used here means organic fatty acids containing four to thirty carbons, and 
may be synthetic or natural, saturated or unsaturated, with straight or 
branched chains. Preferred fatty acids have from 10 to 20 carbons. 
Examples of fatty acids that can be used in this invention are butyric, 
caproic, caprylic, pelargonic, capric, undecanoic, lauric, myristic, 
palmitic, stearic, arachidic, behenic, oleic, linoleic, linolenic, 
eleostearic, and arachidonic acids. Mixtures of fatty acids may also be 
used, such as those obtained from non-hydrogenated or hydrogenated 
soybean, safflower, sunflower, sesame, peanut, corn, olive, rice bran, 
canola, babassu nut, coconut, palm kernel, cottonseed, or palm oils. 
Alternatively, F.sub.1, F.sub.2, and F.sub.2 may be fatty acid derivatives, 
such as, for example, halogenated fatty acids, such as brominated oleic 
acid. Or F.sub.1, F.sub.2, and F.sub.2 may be dicarboxylate-extended fatty 
acid residues. By "dicarboxylate-extended" or "dicarboxylic acid-extended" 
fatty acid residues is meant residues formed from the reaction of fatty 
alcohols with dicarboxylic acids, such as, for example, malonic, succinic, 
glutaric or adipic acid. These resulting malonyl, succinyl, glutaryl or 
adipoyl fatty acid residues are, structurally, aliphatic fatty acids with 
their chains extended by the radicals --OC--CH.sub.2 --CO-- (malonyl), 
--OC--(CH.sub.2).sub.2 --CO-- (succinyl), --OC--(CH.sub.2).sub.3 --CO-- 
(glutaryl), --OC--(CH.sub.2).sub.4 --CO-- (adipoyl), and the like. Thus, 
if a fatty acid residue is denoted by an R', a malonyl- (or 
malonate-extended) fatty acid residue would be R'--O--(CO)--CH.sub.2 
--(CO)--, a succinyl- (or succinate-extended) fatty acid residue would be 
R'--O--(CO)--(CH.sub.2).sub.2 --(CO)--, a glutaryl- (or 
glutarate-extended) fatty acid residue would be 
R'--O--(CO)--(CH.sub.2).sub.3 --(CO)--, and so forth. 
The preferred partially digestible fat mimetics typically provide from 
about 0.5 to 6 kcal/gram. In the preferred compounds, F.sub.1, F.sub.2, 
and F.sub.3 show differential reactivity toward digestive enzymes, so that 
the compounds become more hydrophilic when catabolized. The compounds may 
be engineered so that a digestible residue can be an essential or 
nutritionally desirable fatty acid such as linoleic acid. 
The monomeric and dimeric tris-hydroxymethyl alkane esters of this 
invention may be incorporated either alone, or in combination with another 
fat and/or fat mimetic, into any food composition or used in conjunction 
with any edible material. The term "edible material" is broad and includes 
anything edible. Representative of edible materials which can contain the 
fat mimetic compounds of this invention in full or partial replacement of 
natural fat are: frozen desserts, e.g., sherbet, ice cream, ices, or milk 
shakes; puddings and pie fillings; margarine substitutes or blends; 
flavored bread or biscuit spreads; mayonnaise; salad dressings; filled 
dairy products such as filled cream or filled milk; dairy or non-dairy 
cheese spreads; coffee lighteners, liquid and dried; flavored dips; frying 
fats and oils; reformed and comminuted meats; meat substitutes or 
extenders; whipped toppings; compound coatings; frostings and fillings; 
cocoa butter replacements or blends; candy, especially fatty candies such 
as those containing peanut butter or chocolate; chewing gum; bakery 
products, e.g., cakes, breads, rolls, pastries, cookies, biscuits, and 
savory crackers; mixes or ingredient premixes for any of these; as well as 
flavor, nutrient, drug or functional additive delivery systems. 
The following is a list of representative, but not limiting, examples of 
monomeric and dimeric trishydroxymethyl alkane esters of this invention: 
##STR4##

EXAMPLES 
The following examples are presented to further illustrate and explain the 
present invention and should not be taken as limiting in any regard. 
Unless otherwise indicated, all parts and percentages are by weight (in 
both the synthesis and food recipe examples), and are based on the weight 
at the particular stage of the processing being described. The proton NMR 
spectra have assigned chemical shifts, multiplicities, and intensities 
consistent with the structures with which they are reported. 
EXAMPLE 1 
1,1,1-Tris hydroxymethylethane trioleate (also called 
1,1,1-tris-(oleoyloxymethyl)ethane), a monomeric trishydroxymethyl alkane 
ester of this invention, is synthesized in this example. 
1,1,1-Tris(hydroxymethyl)ethane (12 g., 0.1 mole) is dissolved in 150 mL 
tetrahydrofuran (THF) by warming, and to the solution is added 91 g. (0.3 
mole) of technical grade oleoyl chloride. When gas evolution subsides, 
vacuum (-100 torr) is applied for 15 minutes, then the reaction mixture is 
allowed to stand at ambient temperature and pressure for 16 hours. 
Evaporation of solvent and filtration of the residue through silica (using 
1500 mL hexane) affords 65 g. (71%) of crude product as a yellow oil. 
Proton NMR spectrum in CDCl.sub.3 chemical shift in ppm (multiplicity, 
intensity, assignment): 5.35 (multiplet, 6 H, HC.dbd.CH), 4.01 (singlet, 6 
H, O--CH.sub.2), 2.31 (triplet, 6 H, O.dbd.C--CH.sub.2), 2.02, 1.61 and 
1.29 (multiplets, 72 H, --CH.sub.2 --), 1.01 (singlet, 3 H, --CH.sub.3) 
and 0.87 (triplet, 9 H, --CH.sub.3). 
Analysis: Calculated for C.sub.59 H.sub.108 O.sub.6, FW 913.50: C 77.57, H 
11.92, O 10.51%; Found: C 77.45, H 11.85%. 
EXAMPLE 2 
1,1,1-Tris-hydroxymethylethane distearate/oleate, a one-to-three adduct of 
tris-hydroxymethylethane having a 2:1 ratio of stearic to oleic acids, a 
tris-hydroxymethyl alkane mixed ester of this invention, is synthesized in 
this example. 
A combination of one equivalent tris-hydroxymethyl ethane with two 
equivalents stearoyl chloride and one equivalent oleoyl chloride in 
pyridine affords an oil. 
Proton NMR analysis shows a 1.75/1.25 ratio of saturated to unsaturated 
fatty acid moieties in the product 
EXAMPLE 3 
1,1,1-Tris-hydroxyethane dioleate/stearate, a one-to-three adduct of 
tris-hydroxymethyl ethane and a 2:1 ratio of oleic to stearic acids, 
another mixed trishydroxymethyl alkane ester of this invention, is 
prepared in this example. 
A combination of one equivalent trishydroxymethyl ethane with one 
equivalent stearoyl chloride and two equivalents oleoyl chloride in 
pyridine affords an oil. 
Proton NMR analysis shows a 0.86/2.14 ratio of saturated to unsaturated 
fatty acid moieties in the product. 
EXAMPLE 4 
1,1,1-Tris-hydroxymethylethane tri-9,10-dibromooctadecenate (also called 
1,1,1-tris- (1,10-dibromooctadecanoyloxymethyl)ethane), a substituted 
monomeric trishydroxymethyl alkane ester of this invention, is synthesized 
in this example. 
To 2.0 g. (0.00218 mole) of 1,1,1-tris(oleoyloxymethyl) ethane is added 23 
mL of a solution containing 5% bromine in carbon tetrachloride. After 
standing for 10 minutes, the reaction mixture is concentrated on a rotary 
evaporator to give a yellow oil. 
Proton NMR spectrum in CDCl.sub.3 : chemical shift in ppm (multiplicity, 
intensity, assignment): 4.20 (doublet of doublets, J c. 9 and 3 Hz, 6 H, 
HCBr), 4.01 (singlet, 6 H, CH.sub.2 --O), 2.32 (triplet, 6 H, 
O.dbd.C--CH.sub.2), 2.05 and 1.85 (multiplets, 12 H, CH.sub.2), 
1.6(multiplet, 12 H, CH.sub.2 --C--Br), 1.30 (multiplet, 54 H, CH.sub.2), 
1.02 (singlet, 3 H, ethane CH.sub.3) and 0.87 (triplet, 9 H, CH.sub.3). 
EXAMPLE 5 
1,1,1-tris-hydroxymethylpropane trioleate (also called 
1,1,1-tris-(oleoyloxymethyl)propane), another tris-hydroxymethyl alkane 
ester of this invention, is synthesized in this example. 
A solution of 1,1,1-tris(hydroxymethyl)propane (1.34 g., 0.01 mole), oleoyl 
chloride (10 mL, c. 0.03 mole) and 15 mL pyridine is shaken overnight at 
ambient temperature, then filtered through a short bed of silica gel. The 
filtrate is concentrated on the rotary evaporator to give an oil. 
Proton NMR spectrum in CDCl.sub.3 : chemical shift in ppm (multiplicity, 
intensity, assignment): 5.35 (multiplet, 6 H, HC.dbd.CH), 4.01 (singlet, 6 
H, CH.sub.2 --O), 2.30 (triplet, 6 H, O.sub.2 C--CH.sub.2), 2.01 (broad 
multiplet, 12 H, C.dbd.C--CH.sub.2), 1.60 (multiplet, 6 H, O.sub.2 
C--C--CH.sub.2), 1.47 (quartet, 2 H, propane CH.sub.2), 1.30 (multiplet, 
60 H, CH.sub.2), and 0.87-0.88 (superimposed triplets, 12 H, CH.sub.3). 
EXAMPLE 6 
1,1,1-Tris-hydroxymethylethane tri-10-undecenate (also called 
1,1,1-tris(10-undecenoyloxymethyl)ethane), another trishydroxymethyl 
alkane ester of this invention, is synthesized in this example. 
To a solution of 1.2 g. (0.01 mole) 1,1,1-tris(hydroxymethyl)ethane in 10 
mL pyridine is added 6.5 mL (c. 0.03 mole) 10-undecenoyl chloride. The 
mixture is shaken overnight at ambient temperature, filtered through 
silica (eluted with pentane), and the eluate concentrated to afford an 
oil. 
Proton NMR spectrum in CDCl.sub.3 : chemical shift in ppm (multiplicity, 
intensity, assignment): 5.78 (multiplet, 3 H, HC.dbd.C), 4.95 (multiplet, 
6 H, C.dbd.CH.sub.2), 3.97 (singlet, 6 H, CH.sub.2 --O), 2.29 (triplet, 6 
H, O.dbd.C--CH.sub.2), 2.01 (quartet, 6 H, C.dbd.C--CH.sub.2), 1.59 
(apparent quintet, 6 H, O.dbd.C--C--CH.sub.2), 1.30 (multiplet, 30 H, 
CH.sub.2) and 0.99 (singlet, 3 H, ethane --CH.sub.3). 
EXAMPLE 7 
1,1,1-Tris-hydroxymethyl tri-10-undecenate (also called 
1,1,1-tris-(10-undecenoyloxymethyl)propane), another trishydroxymethyl 
alkane ester of this invention, is prepared in this example 
To a solution of 1.34 g. (0.01 mole) 1,1,1-tris (hydroxymethyl)propane in 
10 mL pyridine is added 6.5 mL (c. 0.03 mole) 10-undecenoyl chloride. The 
mixture is shaken overnight at ambient temperature and filtered through 
silica (eluted with pentane) Concentration of the eluate affords an oil. 
Proton NMR spectrum in CDCl.sub.3 : chemical shift in ppm (multiplicity, 
intensity, assignment): 5.81 (multiplet, 3 H, C.dbd.CH), 4.95 (multiplet, 
6 H, C.dbd.CH.sub.2), 4.01 (singlet, 6 H, CH.sub.2 --OH), 2.29 (triplet, 6 
H, CH.sub.2 --CO.sub.2), 2.02 (apparent quartet, 6 H, C.dbd.C--CH.sub.2), 
1.60 (multiplet, 6 H, CH.sub.2 --C--CO.sub.2), 1.48 (quartet, 2 H, propane 
CH.sub.2), 1.30 (multiplet, 30 H, CH.sub.2) and 0.87 (triplet, 3 H, 
CH.sub.3). 
EXAMPLE 8 
1,1,1-Tris-hydroxymethylethane trisuccinyloleate, a three-to-one adduct of 
monooleyl succinoyl chloride with 1,1,1-tris(hydroxymethyl)ethane, a 
dicarboxylate-extended trishydroxymethyl alkane ester of this invention, 
is prepared in a two-step synthesis in this example. 
Monooleyl succinoyl chloride is first prepared. Oleyl alcohol (59.0 g., 
0.22 mole), 4-dimethylaminopryidine (6.7 g., 0.054 mole), succinic 
anhydride (32.0 g., 0.32 mole) and 400 mL pyridine are combined and 
stirred overnight at ambient temperature. The reaction mixture is then 
diluted with c. 1500 mL water and extracted with ether. The aqueous layer 
is acidified (with concentrated HCl) and extracted with ether. The 
combined extracts are dried over magnesium sulfate, filtered, and 
concentrated on the rotary evaporator to afford a light brown oil This is 
combined with 200 mL thionyl chloride and stirred for 24 hours Evaporation 
of the excess thionyl chloride yields a brown oil 
Proton NMR spectrum in CDCl.sub.3 : chemical shift in ppm (multiplicity, 
intensity, assignment): 5.35 (multiplet, 2 H, HC.dbd.CH), 4.10 (triplet, 2 
H, O--CH.sub.2), 3.21 (triplet, 2 H, CH.sub.2 --COCl), 2.68 (triplet, 2 H, 
CH.sub.2 --CO.sub.2), 2.01 (multiplet, 4 H, C.dbd.C--CH.sub.2), 1.62 
(multiplet, 2 H, O--C--CH.sub.2), 1.30 (multiplet, 22 H, CH.sub.2), and 
0.87 (triplet, 3 H, CH.sub.3). 
This monooleyl succinoyl chloride (13.8 g., 0.36 mole) is then added to a 
solution of 1.32 g. (0.01 mole) 1,1,1-tris(hydroxymethyl)ethane in 15 mL 
pyridine. The mixture is shaken overnight at ambient temperature, filtered 
through silica (eluted with pentane), and the eluate is concentrated on 
the rotary evaporator to give an oil. 
Proton NMR spectrum in CDCl.sub.3 : chemical shift in ppm (multiplicity, 
intensity, assignment): 5.35 (multiplet, 6 H, HC.dbd.CH), 4.06 (triplet, 6 
H, oleyl O--CH.sub.2), 4.01 (singlet, 6 H, ethane C--CH.sub.2 --O), 2.63 
(A2B2 pattern, 12 H, O.dbd.C--CH.sub.2 --CH.sub.2 --C.dbd.O), 2.01 
(multiplet, 8 H, C.dbd.C--CH.sub.2), 1.61 (multiplet, 6 H, oleyl 
O--C--CH.sub.2), 1.30 (multiplet, 66 H, CH.sub.2), 1.02 (singlet 3 H, 
ethane --CH.sub.3), and 0.87 (triplet, 9 H, oleyl CH.sub.3). 
EXAMPLE 9 
1,1,1-Tris-hydroxymethylethane trimyristate (also called 
1,1,1-tris(tetradecanoyloxymethyl)ethane), another trishydroxymethyl 
alkane ester of this invention, is prepared in this example. 
A solution of tris(hydroxymethyl)ethane (1.20 g., 0.01 mole), myristoyl 
chloride (7.38 g., 0.03 mole) and pyridine (25 mL) is shaken at ambient 
temperature overnight. The reaction mixture is filtered, concentrated and 
refiltered through silica gel to afford an oil. 
EXAMPLE 10 
1,1,1-Tris-hydroxymethyl ethane trimyristate (also called 
1,1,1-tris(myristoyloxymethyl) ethane) is prepared in an alternate 
procedure in this example. 
Myristoyl chloride (1000 g., 4.05 mole) is charged to a 2-liter flask 
equipped with a magnetic stirrer bar, thermometer, and a gas outlet which 
is attached to a vacuum source by means of an acid trap (containing 500 g. 
solid NaOH pellets). With stirring, 160 g. (1.33 mole) 1,1,1-tris 
(hydroxymethyl)ethane is added and the slurry is placed under reduced 
pressure (-100 torr) and is warmed by means of a heating mantle. Between 
40.degree. and 80.degree. C. gas (HCl) evolves vigorously from the 
reaction flask, and vacuum may need to be interrupted momentarily to avoid 
reactant carry-over. As gas evolution subsides, the temperature is raised 
to 120.degree. C. (-100 torr), and these conditions are maintained until 
gas evolution is complete. Stirring under vacuum is continued for one 
hour, and the temperature is allowed to fall to about 80.degree. C., 
vacuum is released, and the crude product is passed through a falling film 
still (conditions: 168.degree. C., 0.8 torr) to remove excess fatty acid 
residues. 
The product oil is steam deodorized (conditions: 6 wt. % steam, 
195.degree.-205.degree. C., ca. 0.5 torr). Upon cooling, the colorless oil 
affords a white solid with a melting point of 36.degree.-40.degree. C. The 
yield is quantitative. The titratable acidity (expressed as myristic acid) 
is less than 0.4 wt. %. 
EXAMPLE 11 
1,1,1-Tris-hydroxymethylethane trisuccinylundecenate (also called 
1,1,1-tris(5-oxa-4-oxohexadeca-15-enoyloxymethyl) ethane), another 
dicarboxylate-extended tris-hydroxymethyl alkane ester of this invention, 
is prepared in this example. 
A solution of tris(hydroxymethyl)ethane (1.20 g., 0.01 mole), monoundecenyl 
succinate (8.64 g., 0.03 mole) and pyridine (25 mL) is shaken at ambient 
temperature overnight. The reaction mixture is filtered, concentrated and 
refiltered through silica to afford an oil. 
EXAMPLE 12 
Hexaoleoyldipentaerythritol, a dimeric compound of this invention, is 
prepared in this example. 
A mixture of dipentaerythritol (2.54 g., 0.01 mole), oleoyl chloride (18 
g., 0.06 mole) and pyridine (40 mL) is shaken at ambient temperature 
overnight. The mixture is then filtered, concentrated and refiltered 
through silica to afford an oil. 
EXAMPLE 13 
Hexa(10-undecenoyl)dipentaerythritol, another trishydroxymethyl alkane 
ester dimer of this invention, is synthesized in this example. 
A mixture of dipentaerythritol (2.54 g., 0.01 mole), 10-undecenoyl chloride 
(12.96 g., 0.06 mole) and pyridine (35 mL) is shaken at ambient 
temperature overnight. The mixture is filtered, concentrated and 
refiltered to afford an oil. 
EXAMPLE 14 
This example outlines the procedure for estimating the in vitro 
digestibility of the synthetic fat mimetics of this invention using 
pancreatic lipase. 
Preparation of Reagents and Materials: 
1. Buffer: A pH 7.1 phosphate buffer is prepared by dissolving 6.8 g. 
KH.sub.2 PO.sub.4 in 1 L. of millipore filtered water (to yield 0.05M 
phosphate). Fifty mg. Ca(NO.sub.3).sub.2 and 5.0 g. cholic acid (Na salt, 
an ox bile isolate from Sigma) are added to give 300 microM Ca.sup.++ and 
0.5% cholic acid in 0.05M phosphate. The pH is adjusted to approximately 
7.1 with solid NaOH. Several drops of Baker "Resi-analyzed" toluene are 
added to prevent bacterial growth during storage at 3.degree.-5.degree. C. 
2. Lipase: About 15 mg./mL commercial porcine pancreatic lipase from U.S. 
Biochemical Corporation is dissolved in buffer. 
3. Substrates and Standards: A 1.0 mL volumetric flask is charged with an 
amount of lipid substrate (test substance or standard) calculated to give 
a concentration of 200 nanomoles per microliter in Baker "Resi-analyzed" 
toluene. (The proper concentration may be approximated by doubling the 
molecular weight of the lipid in question, dividing by 10, and diluting to 
the mark; this yields about 200 nanomoles per microliter.) This 
preparation affords the substrate to be used in the hydrolysis reactions. 
Fatty acids and glyceride standards from Nu Chek or Sigma are prepared for 
elution on TLC plates (prewashed with 1:1 chloroform/methanol) by diluting 
the substrate solution with 10:1 toluene (1 part substrate plus 9 parts 
toluene) in septum vials. 
Procedure: 
In a 25 mL Erlenmeyer, emulsify 20 mL buffer and 40 microliters of 
substrate using an ultrasonic disrupter at a microtip maximum setting for 
approximately 10 seconds. This results in a 0.4 microliter/milliliter 
emulsion. Place in a 37.degree. C. water bath and stir vigorously. After 
temperature equilibration, add 40 microliters of enzyme solution and start 
timing. Remove 5.0 mL aliquots at convenient time intervals for analysis. 
To establish a standard curve for triolein, aliquots are taken at 10, 20, 
30 and 40 minutes. A zero time control should be run for all test 
compounds. 
Add the aliquot to a 15 mL glass centrifuge tube containing a drop of 
concentrated HCl. Add approximately 3 mL of a 2:1 mixture of CHCl.sub.3 
:CH.sub.3 OH and shake vigorously. Centrifuge at approximately 5000 rpm 
for 5 minutes and transfer the bottom layer with a Pasteur pipet to a 5 mL 
septum vial. Repeat the extraction step once and combine the two bottom 
layers. Evaporate the solvent in nitrogen gas. After about half of the 
solvent is removed, add an equivalent volume absolute ethanol and continue 
evaporation in a nitrogen stream until dryness is achieved. Samples may be 
warmed with a heat gun to facilitate drying. 
When the samples are dry, add exactly 200 microliters of toluene containing 
10% DMSO, cap tightly, and spot TLC plate with 2.0 microliters per 
channel. (If 100% extraction efficiency of a zero time control, this 
amounts to 20 nanomoles of substrate spotted on the plate.) Develop with a 
suitable solvent system, for example, hexane:ethyl ether:acetic acid in a 
ratio of 60:40:1. After 15 cm elution, dry plate with a heat gun and 
determine amounts of starting substrate and products of hydrolysis by 
scanning 10 to 20 nanomoles per channel at a wavelength of 190 nm using 
the CAMAG TLC Scanner II densitometer equipped with a Spectra Physics 4270 
integrator and comparing with controls run at the same time. 
Results: 
Using this procedure with the 1,1,1-tris-hydroxymethyl ethane trioleate 
prepared in Example 1, limited hydrolysis is observed after three hours 
contact with pancreatic lipase. Using a triglyceride control, triolein is 
substantially hydrolyzed in 10 minutes with this enzyme system. 
EXAMPLE 15 
This example illustrates how the novel fat mimetics of this invention are 
screened for caloric availability by a carefully controlled in vivo animal 
feeding study. 
An experimental relationship between total calories ingested and animal 
body weight gain is established by monitoring the body weight gain 
associated with consumption of a nutritionally balanced diet containing 
varying concentrations of a reference substance such as corn oil which has 
a known caloric availability. Correlations between total calories ingested 
and body weight gain are excellent (r=0.99). 
Caloric availability of an unknown substance is evaluated by substituting a 
specific weight of the unknown substance for the reference substance and 
observing the body weight gain. The gain in body weight is equated to a 
total number of calories using the correlation previously established for 
the reference data. The estimated number of calories ingested are divided 
by the weight of unknown substance to give the apparent calories per gram 
for the unknown substance. Generally speaking, in these bioavailability 
studies, the degree of perianal pelt soiling correlates with reduced 
bioavailability. 
The test animals are six-week-old male Sprague-Dawley rats obtained from 
the Portage, Mich. facility of the Charles River Laboratories, Inc. After 
acclamation for 15 days, the test duration is 14 days. The dietary 
requirements are established by observing the actual feed consumption of 
animals provided with unlimited feed. All diets are prepared to contain 
50% of the established dietary requirements plus any supplements of 
reference or unknown substances. In all tests so designed the test animals 
are maintained in very good health. 
The test feeds are AIN-76A and fortified AIN-76A (hereinafter abbreviated 
"fort") AIN-76A (Teklad). The major components of these diets are as 
follows: 
______________________________________ 
component AIN-76A fortified AIN-76A 
______________________________________ 
casein 20% 40% 
corn starch 15 8.08 
sucrose 50 26.02 
fiber 5 5 
corn oil 5 5 
AIN mineral mix 
3.5 7 
AIN vitamin mix 
1 2 
choline 0.2 0.4 
methionine 0.3 0.6 
total 100% 100% 
calc. caloric density 
3.85 kcal/gm 
3.9 kcal/gm 
______________________________________ 
Using these diets supplemented by reference or test substances fed as 
microencapsulated oils, sample body weight (hereinafter abbreviated "wgt") 
gains for example animals A and B fed corn oil as a reference (9.0 
calories/gram) are as follows: 
______________________________________ 
Animal A Animal B 
calor- calor- 
ories ories 
diet wgt gain con- wgt gain 
con- 
supplied (grams) sumed (grams) 
sumed 
______________________________________ 
ad lib AIN-76A 73.6 1275 82.4 1370 
50% fort -3.4 651 -3.8 691 
50% fort + 7.75% gelatin 
9.0 705 8.3 747 
50% fort + 7% corn oil 
13.9 768 15.2 831 
50% fort + 14% corn oil 
28.3 913 37.9 998 
50% fort + 21% corn oil 
57.7 1093 63.3 1183 
______________________________________ 
The rats were fed a diet of 50% fort and 21% 1,1,1-tris hydroxymethylethane 
trioleate prepared in Example 1 as a test compound under the foregoing 
procedure, and their weight gain was determined. Using the base line 
control data and the data from the test compound, it was determined that 
1,1,1-tris hydroxymethylethane trioleate gave about 3.3 kcal/gram upon 
being metabolized. 
EXAMPLE 16 
Milk Chocolate. In this example, a synthetic fat mimetic of this invention 
prepared in Example 9 is used to prepare low calorie milk chocolate. 
Equal parts of cocoa powder, sugar and fat mimetic are mixed in a glass 
beaker and are incubated with frequent stirring at 65.degree. C. until a 
smooth, uniform fudge-like mixture is obtained. Lecithin, which is 
normally added at about 0.5% to chocolate and palm kernel oil to lower 
viscosity, is unnecessary since the viscosity of the fat mimetic is well 
suited to pouring into molds or enrobing. The hot mixture is poured into 
molds and quench cooled by placing in a freezer at approximately 
-10.degree. C. No tempering regimen is necessary. 
EXAMPLE 17 
Filled Cream. About 18 Kg of a fat mimetic of Example 3 may be homogenized 
with 82 Kg of skim milk in a conventional dairy homogenizer to afford a 
"filled cream" composition. 
EXAMPLE 18 
Ice Cream. The "filled cream" composition of Example 17 (68 parts) may be 
combined with 15 parts condensed skim milk, 15 parts sugar, 0.5 parts 
gelatin, 1.0 part flavor, and 0.25 parts color to produce an ice cream mix 
which is processed in the normal manner to yield a modified ice cream 
product. 
EXAMPLE 19 
Filled Milk. About 100 parts of the filled cream composition prepared in 
Example 17 may be combined with about 620 parts of skim milk to prepare a 
"filled milk" composition. 
EXAMPLE 20 
Cheese Products. The filled milk product obtained in Example 17 may be 
treated like natural milk in the normal cheese making process (as is 
practiced, for example in the production of cheddar or swiss cheese). 
Preferably 10% butter oil is added to the fat mimetic portion of the 
filled milk product before it is employed in this process to enhance the 
proper flavor development of the cheese products. 
EXAMPLE 21 
Butter cream icing may be prepared by blending: 
______________________________________ 
Ingredient g. 
______________________________________ 
Sugar 227.0 
Fat mimetic of Example 9 
70.8 
Water 28.4 
Non-Fat Dry Milk 14.0 
Emulsifier 1.4 
Salt 1.0 
Vanilla 1.0 
______________________________________ 
All of the ingredients are creamed in a mixer at medium speed. 
EXAMPLE 22 
Vanilla Wafers. Twenty-five parts of a fat mimetic of Example 5 may be 
blended with 100 parts flour, 72 parts granulated sugar, 5 parts high 
fructose corn syrup, 1 part non-fat dry milk, 1 part salt, 1/10 part 
ammonium bicarbonate, 1 part dried egg yolk, 1/10 part sodium bicarbonate, 
and 55 parts water. The dough so formed may be rolled, wire cut to 1/4 
inch thickness, and baked by the usual process to give a vanilla wafer 
cookie. 
EXAMPLE 23 
Sugar Cookies. Sugar cookies may be prepared by blending: 
______________________________________ 
Ingredient g. 
______________________________________ 
Sugar 231 
Fat Mimetic of Example 3 
114 
Salt 3.7 
Sodium Bicarbonate 4.4 
Water 37.4 
5.9% Dextrose Solution (wt/wt) 
58.7 
Flour 351 
______________________________________ 
All of the ingredients are creamed together. The dough so formed may be 
extruded (the dough is very tacky) and baked by the usual process. 
EXAMPLE 24 
Sprayed Crackers. A dough prepared from 100 parts flour, 5 parts sugar, 1.5 
parts malt, 7.5 parts of the fat mimetic prepared in Example 5, 1 part 
salt, 0.9 parts sodium bicarbonate, 2.5 parts non-fat dry milk, 2.5 parts 
high fructose corn syrup, 0.75 parts monocalcium phosphate, and 28 parts 
water is sheeted, stamped, and baked to produce a cracker product. 
The above descriptions are for the purpose of teaching the person of 
ordinary skill in the art how to practice the present invention, and it is 
not intended to detail all those obvious modifications and variations of 
it which will become apparent to the skilled worker upon reading the 
description. It is intended, however, that all such obvious modifications 
and variations be included within the scope of the present invention, 
which is defined by the following claims.