Sulfur extrusion with tin radical: synthesis of 4',5'-didehydro-5'-deoxy-5'-(tributylstannyl)adenosine, an intermediate for potential inhibitors against S-adenosyl homocysteine hydrolase.
A new approach has been developed for the synthesis of potential inhibitors of S-adenosyl-l-homocysteine (AdoHcy) hydrolase. The key intermediate 9-[2,3-bis-O-(tert-butyldimethylsilyl)-5-(Z)-(tributylstannyl)-5-deoxy-beta-d-erythro-pent-4-enofuranosyl]adenine (12) was prepared by sulfur extrusion reaction of 4',5'-didehydro-5'-deoxy-5'-(phenylthio)adenosine (11) with tributyltin radical. It was found that this reaction proceeds stereoselectively, forming 12 irrespective of the geometry of 11. Compound 12 readily underwent iodination, bromination, and chlorination with retention of configuration, whereas fluorination gave both (Z)- and (E)-isomers of vinyl fluoride. Because of the susceptibility of 12 to protodestannylation, the (Z)-vinyl iodide (13), prepared in quantitative yield from 12, was used as a substrate for C-C bond formation. Various types of carbon substituents (phenyl, vinyl, trifluorovinyl, ethynyl, and cyano) were introduced to the 5'-position of the 5-deoxy-beta-d-erythro-pent-4-enofuranosyl structure to open up a new route to potential inhibitors of AdoHcy hydrolase.
Kumamoto
Hiroki
H
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Onuma
Sayoko
S
Tanaka
Hiromichi
H
D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet; D013455:Sulfur / Q000737:chemistry*; D014001:Tin / Q000737:chemistry*
C484680:4',5'-didehydro-5'-deoxy-5'-(tributylstannyl)adenosine; D004791:Enzyme Inhibitors; D013455:Sulfur; D014001:Tin; D043383:Adenosylhomocysteinase; D000241:Adenosine