Method of preparation of alpha galactosyl ceramides compounds

A method of preparation of a compound of formula (I):

• said method comprising:
• a) glycosylating a compound of formula (II):
• with a compound of formula (III):
• thereby producing a compound of formula (IV):
• wherein:
• R1 represents a linear or branched, saturated or unsaturated C1-C20 alkyl group;
• R2 represents a linear or branched, saturated or unsaturated C1-C30 alkyl group;
• R3 represents C1-C6 alkyl, a C3-C6 cycloalkyl, a C1-C6 acyl or a benzoyl group;
• and R4 represents H or C1-C6 alkyl group;
• or
• R3 and R4 form together with the nitrogen atom to which they are attached a C2-C6 heterocycloalkyl group or a C1-C5 heteroaryl group;
• PG1 represents a hydroxyl function protecting group;
• PG2 represents a primary amine function protecting group selected from the group consisting of carboxybenzyl (Cbz), p-methoxybenzyl carbonyl (Moz or MeOZ), tert-butyloxycarbonyl (BOC), 9-fluorenylmethyloxycarbonyl (FMOC), acetyl (Ac), benzoyl (Bz), benzyl (Bn), carbamate groups, p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts) and other sulfonamides (Nosyl & Nps) groups;
• PG3 represents a hydroxyl function protecting group;
• PG′3 represents a hydroxyl function protecting group;
• and
• LG represents a leaving group;
• and
• said method further comprising, after step a):
• b) deprotecting protecting groups PG1 and PG2 of the compound of formula (IV), said step b) providing a compound of formula (V):
• wherein R1, R3, R4, PG3 and PG′3 are as defined above, and
• c) coupling the compound of formula (V) with a compound of formula R2COCl (VII), wherein R2 represents a linear or branched, saturated or unsaturated C1-C30 alkyl group, in the presence of a base;
• and
• d) deprotecting protecting groups PG3 and PG′3 of the product obtained in step c);
• said steps providing a compound of formula (I);
• or
• b′) deprotecting protecting groups PG1, PG2, PG3 and PG′3 of compound of formula (IV), said step b′) providing a compound of formula (VI):
• wherein R1, R3 and R4 are as defined above;
• and
• c′) coupling the compound of formula (VI) with a compound of formula R2COCl (VII), wherein R2 represents a linear or branched, saturated or unsaturated C1-C30 alkyl group, in the presence of a base, said step c′) providing a compound of formula (I);
• to produce the compound of formula (I),
• wherein the method comprises no less than two and no more than two steps of purification by silica-gel column chromatography.