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Highly Concise Synthesis of 3'‐"Up"‐ethynyl‐5'‐methylbicyclo‐ [3.1.0]hexyl Purine and Pyrimidine Nucleoside Derivatives Using Rhodium(II) Carbenoid Cycloaddition and Highly Diastereoselective Grignard Reaction
Author(s) -
Yang Zunhua,
Kim Kyung Ran,
Park AhYoung,
Lee HyungRock,
Kang JinAh,
Kim Won Hee,
Chun Pusoon,
Gong Ping,
Lee Boeun,
Jeong Lak Shin,
Moon Hyung Ryong
Publication year - 2009
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201090016
Subject(s) - chemistry , carbenoid , alkylation , pyrimidine , purine , nucleoside , uracil , steric effects , stereochemistry , rhodium , bromide , nucleobase , medicinal chemistry , organic chemistry , catalysis , dna , biochemistry , enzyme
Synthesis of north ‐5'‐methylbicyclo[3.1.0]hexyl purine and pyrimidine nucleosides with an ethynyl group at C‐3' position has been successfully accomplished by a facile method. Methylbicyclo[3.1.0]hexanone (±)‐ 5 having three contiguous chiral centers was remarkably simply constructed only by four steps containing a carbenoid insertion reaction in the presence of rhodium(II) acetate dimer and CuSO 4 , giving a correct relative stereochemistry of the generated three chiral centers. Upon Grignard reaction of (±)‐ 5 with ethynylmagnesium bromide, exclusive diastereoselectivity was observed. Condensation of glycosyl donor (±)‐ 9 with purine nucleobase afforded only the desired N 9 ‐alkylated nucleoside, while condensation with pyrimidine, N 3 ‐benzoylated uracil gave the desired N 1 ‐alkylated nucleoside (±)‐ 13 with the undesired O 2 ‐alkylated nucleoside (±)‐ 14 . Probably, (±)‐ 14 would be formed due to steric hindrance caused upon approaching for N 1 ‐alkylation.