Synthesis of the Antitumor Agent Aglycon (±)-Calicheamicinone Using an o-Quinone Monoketal Strategy

Autor:	Ian Churcher, David Hallett, Philip Magnus
Rok vydání:	1998
Předmět:	chemistry.chemical_classification Alcohol General Chemistry Biochemistry Aldehyde Medicinal chemistry Enol Catalysis Adduct chemistry.chemical_compound Colloid and Surface Chemistry chemistry Enediyne Protecting group Derivative (chemistry) Lactone
Zdroj:	Journal of the American Chemical Society. 120:10350-10358
ISSN:	1520-5126 0002-7863
Popis:	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 12α- and 12β-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 Ph2SNH 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).
Databáze:	OpenAIRE
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