Patent GB-762540-A (GB)
Title: Improvements relating to the production of 3-amino-3-deoxypentoses and derivatives thereof
IPC: C07H15/18
Filed: 1954-07-13
Abstract: The invention comprises 3-amino-3-deoxypentose compounds of the general formula <FORM:0762540/IV(b)/1> wherein R1 is alkyl or aralkyl, R2 is H, Acyl or R111SO2, R3 is NH2 or NHAcyl, and R4 is H, CH2OH, CH2OAcyl or CH2O3SR111 (R111 being a hydrocarbon radical of not more than 7 carbon atoms), and wherein n is 1 when R4 is H (pyranosides) and zero when R4 is CH2OH, CH2OAcyl or CH2O3SR111 (furanosides).  These compounds may be prepared by the following processes: (a) compounds in which R2=H, R3=NH2 and either R4=H and n=1 or R4= CH2OH and n=O, by reacting 2 : 3-anhydropentosides with ammonia at a temperature from about 25 DEG  to 200 DEG  C.; (b) N-acyl derivatives of the products of (a) by alkaline saponification (with simultaneous reversal of the spatial relationship of the 2- and 4-substituents in the case of the pyranosides and of the 2-substituent in the case of the furanosides) of compounds in which R2=R111SO2, R3=NHAcyl and either R4=H and n=1 or R4=CH2O3SR111 and n=O, the reaction being preferably effected at a temperature from about 80 DEG  to 200 DEG  C. in an inert solvent; (c) the starting materials of (b) by treating the products of (a) with an acylating agent to acylate the amino group and then with a sulphonyl halide R111SO2X (X=halogen) to esterify the two free hydroxy groups; and, in general, by various hydrolysis or acylation reactions to effect selective replacement of one or more of the groups R1, R2, R3, R4. The products (of which those in which R3=NH2 form salts with acids such as hydrochloric, sulphuric, acetic and citric acid) are useful as intermediates for the preparation of compounds acting as antagonists to Vitamins B2 and B12 and of compounds having antibiotic activity.  Thus antagonists to Vitamin B2 are obtainable by triacetylating a 3-amino-3-deoxypyranoside, treating the triacetyl derivative with acetic anhydride and sulphuric acid to replace the group R1 with an acetyl group, and treating the product with methanolic sodium methoxide or methanolic ammonia to produce the corresponding 3-acetylamino-3-deoxypentose, which is then employed in place of D-ribose in the standard synthesis of riboflavin.  In examples: (1) b -methyl 2 : 3-anhydro-L-ribopyranoside is heated with aqueous ammonia under pressure to produce b -methyl 3-amino-3-deoxy-L-xylopyranoside; (2) the product of (1) is triacetylated with acetic anhydride and pyridine, the triacetyl derivative is treated with acetic anhydride and sulphuric acid to produce 3-acetylamino - 3 - deoxy - L - xylopyranoside triacetate, and this is refluxed with methanolic sodium methoxide to give 3-acetylamino-3-deoxy-L-xylose; (3) a - or b -methyl 2 : 3-anhydro-D-lyxofuranoside is treated as in (1) to form a - or b -methyl 3 - amino - 3 - deoxy - D - arabinofuranoside (isolated as their N-isopropylidene derivatives by solution in acetone); (4) and (5) aqueous solutions of the N-isopropylidene products of (3) are treated with acetic anhydride to produce a - and b -methyl 3-acetylamino-3-deoxy-D-arabinofuranoside; (6) b -methyl 2 : 4-dimesyl - 3 - acetylamino - 3 - deoxy - L - xylopyranoside is refluxed with anhydrous sodium acetate in 95 per cent 2-methoxyethanol to yield a -methyl 3-acetylamino-3-deoxy-D-ribopyranoside, which is diacetylated with acetic anhydride and pyridine; (7) the final product of (6) is refluxed with dilute hydrochloric acid to give 3-amino-3-deoxy-D-ribose hydrochloride; (8) a -methyl 2 : 5-dimesyl-3-acetylamino-3-deoxy-D-arabinofuranoside is treated as in (6) to produce a -methyl 3-acetylamino-3-deoxy-D-ribofuranoside and its diacetate; (9) b -methyl 2 : 5-dimesyl - 3 - acetylamino - 3 - deoxy - D - arabinofuranoside similarly yields b -methyl 3-acetylamino - 3 - deoxy - D - ribofuranoside diacetate; (10) and (11) b - and a -methyl 3-acetylamino-3-deoxy-D-ribofuranoside are dibenzoylated with benzoyl chloride and pyridine; (12) and (13) the products of (6) and (8) are refluxed with methanolic sodium methoxide to form a -and b -methyl 3-acetylamino-3-deoxy-D-ribofuranosides; (14) an aqueous solution of b -methyl 3-amino-3-deoxy-L-xylopyranoside is treated with acetic anhydride to form the N-acetyl derivative; (15) the product of (14) is treated with methanesulphonyl chloride and pyridine to produce the starting material of (6); (16) and (17) a - and b -methyl 3-acetylamino-3-deoxy-D-arabinofuranoside similarly yield the starting materials of (8) and (9).  Additional meanings specified for the various symbols are: R1 : ethyl, isopropyl, benzyl, p-methylbenzyl; R3 : formylamino, benzoylamino, ethoxy- and methoxy-carbonylamino; R111 : ethyl, phenyl, p-tolyl.  References are also made to isomers of the products of some of the examples. Starting materials: a - and b -methyl 2 : 3-anhydro-D-hyxofuranosides are obtained from crude methyl D-eylofuranoside by treating it with acetone in the presence of copper sulphate and sulphuric acid, separating the a - and b -isomers of the resulting 3 : 5-isopropylidene compound by fractional distillation, esterifying each isomer with methanesulphonyl chloride and pyridine, and warming the products with aqueous acetic acid, followed by treatment with methanolic sodium methoxide.