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Synthesis of dual 14 C‐labeled (+)‐calanolide A, a naturally occurring anti‐HIV agent
Author(s) -
Gaddam Subbareddy,
Khilevich Albert,
Filer Crist,
Rizzo John D.,
Giltner Jeremey,
Flavin Michael T.,
Xu ZeQi
Publication year - 1997
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199711)39:11<901::aid-jlcr39>3.0.co;2-h
Subject(s) - chemistry , diastereomer , acetaldehyde , yield (engineering) , kinetic resolution , human immunodeficiency virus (hiv) , stereochemistry , coumarin , organic chemistry , catalysis , enantioselective synthesis , materials science , ethanol , metallurgy , medicine , family medicine
[10,18‐ 14 C]‐(+)‐Calanolide A [(+)‐ 6 ] was synthesized in four steps from chromeno‐coumarin 2 . A Ti‐mediated aldol reaction of 2 with [1,2‐ 14 C]‐acetaldehyde stereoselectively produced the desired syn diastereomer (±)‐ 3 , with carbons at the 13 and 14 positions being 14 C‐labeled. Intermediate (+)‐ 3 was isolated by lipase‐catalyzed kinetic resolution and cyclized under Mitsunobu conditions to afford (+)‐ trans ‐2,3‐dimethyl chroman‐4‐one, (+)‐ 5 . Luche reduction on (+)‐ 5 in EtOH/THF at −78°C led to the formation of dual 14 C‐labeled (+)‐ 6 with a specific activity of 49.25 mCi/mmol. The overall radiochemical yield was 4.3% based on the starting 14 C‐acetaldehyde. © 1997 John Wiley & Sons, Ltd.