Journal of the American Chemical Society, Vol.120, No.40, 10350-10358, 1998
Synthesis of the antitumor agent aglycon (+/-)-calicheamicinone using an o-quinone monoketal strategy
Commercially available 5-methoxysalicylic acid 16 was converted into the o-quinone monoketal 21, which was attached to the enediyne 22, resulting in 23. After protection of the tert-alcohol 24 and conversion of the ester 25 to aldehyde 28, treatment with LiN(TMS)(2) gave a 1:4 mixture of the 12 alpha-and 12 beta-ols 29 and 30, respectively. Oxidation of the mixture 29/30 followed by DIBAL-H reduction resulted in exclusive formation of 29. Deprotection of 29 gave 34, which on treatment with Ph2S=NH gave the 2-amino adduct 35. Protection of 35 as the tris-Boc derivative 37 followed by intermolecular Wadsworth-Emmons reaction gave the lactone 38. The lactone 38 was converted into the bis-methyl carbamate derivative 52, which was reduced with NaBH4/CeCl3 to give 55. Conversion of the allylic alcohol 55 into the thiol acetate 58 and then to the trisulfide 61 followed previous precedent. Finally, removal of the enol Boc protecting group and the alcohol protecting groups gave (+/-)-calicheamicinone (2).
Keywords:CORE STRUCTURE, NEOCARZINOSTATIN CHROMOPHORE, ABSOLUTE-CONFIGURATION, KEDARCIDIN CHROMOPHORE, C-1027 CHROMOPHORE;BIOACTIVE ANALOGS, ANTIBIOTICS, CHEMISTRY, ENEDIYNE;CONSTRUCTION