北海道大学 大学院農学院 修士論文発表会，2016 年 2 月 10 日

Halogenated sucrose at the primary position:
Comprehensive structure elucidation and reactivity study(スクロース１級水酸基のハロゲン化：網羅的構造検討と反応性検討)
Division of Applied Bioscience, The Special Postgraduate Program in Biosphere
Sustainability Science, Molecular and Ecological Chemistry Laboratory
Zetryana Puteri Tachrim
1. Introduction
Regioselective halogenation of sucrose′s primary alcohols (at 6-, 6′- or 1′-position) is one of the priorapproaches to simplicity synthesis of carbohydrate-based products. Appel reaction—by the used of carbon
tetrahalide and triphenylphosphine—is one of the efficient methods to directly convert primary hydroxyl
groups to halide. The former subjection of sucrose within limited proportion of Appel reagents gave obscureresults between the selectivity of 6- and 6′-alcohols. For decades, halodeoxysucrose derivatives at the primary
position have been successfully synthesized. But, the detail reported analyses, especially NMR
characterization, have not been completely established. Therefore, the focus of this study is to re-subject
sucrose into Appel reaction to archive regioselective halogenations and then fully construct structural
elucidation of each compound to indentify sucrose reactivity of this reaction.

2. Methods
Re-subjection of sucrose into Appel reaction was conducted using 1.2 equiv. carbon tetrahalide (bromide orchloride) and 2.4 equiv. triphenylphosphine, which followed by acetylation (Scheme 1). All compounds wereassigned by analysis of one- (1H and 13C) and two-dimensional (COSY, HETCOR, HMQC, HMBC, andNOESY) NMR spectroscopy, optical rotation, and mass spectroscopy. Comparison with the literature data for
all compounds also described to support the comprehensive structural elucidation.
HO6HOHO1HOO1'1) 1.2 equiv. CX4 (X= BrR1or Cl), 2.4 equiv. PPh 3,pyridine, 1.5 h, 60 °C AcOOHOHO OOH

6'OH2) Ac2O, rt,overnight

AcO

62 R1 = OAc, R2 = Br (7%)
3 R1 = Br, R2 = OAc (12%)
4 R1 , R2 = Br (7%)
5 R1 = OAc, R2 =Cl (8%)
6 R = Cl, R = OAc (13%)
AcO O
R2 7 R1 , R = Cl2 (5%)
126'
8 R1 , R2 = OAc
OAc
AcOO

1' OAcO

Scheme 1. Regioselective halogenation of sucrose at the 6 and/or 6′ positions by Appel reactions (2–7).

3. Results and Discussions

H-1′
H-6aH-6′
H-6bThe series of per-O-acetylated dihalogenated and2
monohalogenated at 6- and/or 6′-position (2–7; Scheme 1)
H-1′
were obtained. The specific splitting pattern in the upfiled
H-6′
1
region of H NMR (Fig. 1), differentiate the substitution site
3H-6a H-6bof each compound. The 1′-monohalogenated sucrose wasppm
thenexclusively
synthesizedvia
regioselective
4.50
4.00
3.50
chemoenzymatic deacetylation. Thus, allowing the extensive
1
NMR analyses of all monohalogenated sucrose at the primary Figure 1. Selected H NMR signals ofpositions. Further subjection of Appel reaction to 1′-kestose, monobrominated sucrose derivatives at 6- and 6′differs only by the linkage from the second D-fructosyl position (2 and 3).
group to the sucrose, supports the identification of the most hindered and less reactive position through Appelreaction. However, the regioselective Appel reaction of sucrose′s primary alcohols followed the halogenation
order of 6>6′>>1′.

4. Conclusions
Based on comprehensive NMR analyses, previous misinterpreted assignment (Eur. J. Org. Chem. 2007,3655–3668.) of 6′-bromo-6′-deoxysucrose heptaacetate (2) was then revised to 6-bromo-6-deoxysucrose
heptaacetate (3). The complete structural elucidation of each monohalogenated sucrose at the primary position
identified sucrose reactivity by limited proportion of Appel reagents followed the order of 6>6′>>1′.
ref.) Z. P. Tachrim, et al., ChemistrySelect, 2016, 1, 58–62.