Method for inhibition of cell motility by sphingosine-1-phosphate, its derivatives and mimetics and method of synthesizing sphingosine-1-phosphate and its derivatives

A method for chemically synthesizing sphingosine-1-phosphate comprising:

• (A) esterifying the C-3 hydroxyl group of compound 1' to give compound 2' ##STR1## wherein X represents a moiety that protects the amino group formed in step (B),
• (B) selectively deprotecting the C-1 hydroxyl group of said compound 2' to give compound 3' ##STR2## (C) phosphorylating the C-1 hydroxyl group of said compound 3', followed by, hydrolyzing to give compound 4' ##STR3## (D) deprotecting the C-3 hydroxyl group and the amino group, respectively, of said compound 4' to give compound 1, which is said sphingosine-1-phosphate ##STR4##

A method for chemically synthesizing N, N-dimethyl-sphingosine-1-phosphate comprising:

• (A) esterifying the C-3 hydroxyl group of compound 1' to give compound 2' ##STR5## wherein X represents a moiety that protects the amino group formed in step (B),
• (B) selectively deprotecting the C-1 hydroxyl group of said compound 2' to give compound 3' ##STR6## (C) eliminating the protecting moiety X from said compound 3' and then subjecting the product to reductive methylation to give compound 3.sup.a ##STR7## (D) phosphylating the C-1 hydroxyl group of said compound 3.sup.a followed by hydrolyzing to give compound 3.sup.b ##STR8## (E) deprotecting the C-3 hydroxyl group to give compound 2, which is said N,N-dimethyl-sphingosine-1-phosphate ##STR9##

A method for chemically synthesizing N,N,N-trimethyl-sphingosine-1-phosphate comprising:

• (A) esterifying the C-3 hydroxyl group of compound 1' to give compound 2' ##STR10## wherein X represents a moiety that protects the amino group formed in step (B),
• (B) selectively deprotecting the C-1 hydroxyl group of said compound 2' to give compound 3' ##STR11## (C) eliminating the protecting moiety X from said compound 3' and then subjecting the product to reductive methylation to give compound 3.sup.a ##STR12## (D) permethylating said compound 3.sup.a followed by treating with a basic anion exchange resin to give compound 3.sup.h ##STR13## (E) phosphylating the primary hydroxyl group of said compound 3.sup.h followed by hydrolyzing and then deprotecting the C-3 hydroxyl to give compound 3, which is said N,N,N-trimethyl-sphingosine-1-phosphate ##STR14##

A method for chemically synthesizing N-acyl and N-acetylsphingosine-1-phosphate comprising:

• (A) esterifying the C-3 hydroxyl group of compound 1' to give compound 2' ##STR15## wherein X represents a moiety that protects the amino group formed in step (B),
• (B) selectively deprotecting the C-1 hydroxyl group of said compound 2' to give compound 3' ##STR16## (C) eliminating the protecting moiety X, and then acylating or acetylating the unprotected amino group to give compound 3.sup.i ##STR17## wherein Ac represents acyl or acetyl, (D) phosphylating the C-1 hydroxyl group of said compound 3.sup.i, followed by hydrolyzing to give compound 3.sup.j ##STR18## (E) deprotecting the C-3 hydroxyl group to give compound 4, which is said N-acyl or N-acetylsphingosine-1-phosphate ##STR19##