Synthesis of 1-Deoxysphingosine Derivatives with Conformationally Restricted Pyrrolidinediol Head Groups

• Published in: Organic letters Vol. 8; no. 4; pp. 649 - 652
• Main Authors: Dougherty, Ann M, McDonald, Frank E, Liotta, Dennis C, Moody, Steven J, Pallas, David C, Pack, Carrie D, Merrill, Alfred H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.02.2006; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Cyclization; Molecular Structure; Physical Sciences; Pyrrolidines - chemical synthesis; Pyrrolidines - chemistry; Science & Technology; Sphingosine - analogs & derivatives; Sphingosine - chemical synthesis; Sphingosine - chemistry; Stereoisomerism; CELLS; BASES; ASYMMETRIC-SYNTHESIS; INHIBITION; RING-CLOSING METATHESIS; AMINES; IMINES; SPHINGOSINE; EFFICIENT
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol052839v

A family of cyclic 1-deoxysphingolipid derivatives of structure 4 has been designed and synthesized, which may serve as tumorigenesis suppressors for various cancers. Compound 4 is a second-generation analogue developed from sphingosine (1), in which a hydroxyl substituent is moved from C1 to C5 and a methylene is added for conformational rigidity between the C2-nitrogen substituent and C4. The synthetic chemistry for pyrrolidine ring closure at C3−C4 features ring-closing metathesis followed by hydroboration-oxidation.