Synthesis of 1-deoxysphingosine derivatives with conformationally restricted pyrrolidinediol head groups.
[structure: see text] 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.
Dougherty
Ann M
AM
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
McDonald
Frank E
FE
Liotta
Dennis C
DC
Moody
Steven J
SJ
Pallas
David C
DC
Pack
Carrie D
CD
Merrill
Alfred H
AH
D003500:Cyclization; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
C514304:1-deoxysphingosine; D011759:Pyrrolidines; D013110:Sphingosine