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Total Synthesis of (+)‐Blasticidin S
Author(s) -
Ichikawa Yoshiyasu,
Hirata Keiko,
Ohbayashi Masayoshi,
Isobe Minoru
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200305358
Subject(s) - chemistry , yield (engineering) , total synthesis , amide , stereochemistry , stereoselectivity , amine gas treating , glycosylation , organic chemistry , catalysis , biochemistry , materials science , metallurgy
The first total synthesis of the peptidyl nucleoside antibiotic, blasticidin S ( 1 ), has been achieved by the coupling reaction of cytosinine ( 3 ) and blastidic acid ( 2 ). A key step in the synthesis of cytosinine ( 3 ) is the sigmatropic rearrangement of allyl cyanate 24 ; this reaction provided efficient and stereoselective access to 2,3‐dideoxy‐4‐amino‐ D ‐hex‐2‐enopyranose ( 26 a ). Further elaboration of 26 a gave methyl hex‐2‐enopyranouronate 29 , and cytosine N‐glycosylation of 31 using the Vorbrüggen conditions for the silyl Hilbert–Johnson reaction furnished the differentially protected cytosinine ( 32 ) in 11 steps from 2‐acetoxy‐ D ‐glucal ( 14 ) (4.0 % overall yield). Synthesis of the Boc‐protected blastidic acid 47 in nine steps starting from chiral carboxylic acid 35 (23 % overall yield) utilized Weinreb's protocol for the preparation of benzyl amide 38 and Fukuyama's protocol for the synthesis of the secondary amine 40 . Assembly of the protected cytosinine ( 32 ) and blastidic acid ( 47 ) by the BOP method in the presence of HOBt, and finally elaboration to 1 by deprotection of the fully protected 54 established the total synthesis of blasticidin S ( 1 ).