ChemInform Abstract: Total Synthesis of seco-(+)- and ent-(-)-Oxaduocarmycin SA: Construction of the (Chloromethyl)indoline Alkylating Subunit by a Novel Intramolecular Aryl Radical Cyclization onto a Vinyl Chloride.
✍ Scribed by V. F. PATEL; S. L. ANDIS; J. K. ENKEMA; D. A. JOHNSON; J. H. KENNEDY; F. MOHAMADI; R. M. SCHULTZ; D. J. SOOSE; M. M. SPEES
- Publisher
- John Wiley and Sons
- Year
- 2010
- Weight
- 39 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0931-7597
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✦ Synopsis
Total Synthesis of seco-(+)-and ent-(-)-Oxaduocarmycin SA: Construction of the (Chloromethyl)indoline Alkylating Subunit by a Novel Intramolecular Aryl Radical Cyclization onto a Vinyl Chloride.
-The seco-(+) title compound (IX) is an analogue of the highly cytotoxic natural product duocarmycin SA, the newest member of a class of potent antitumor antibiotics. The key-step in the 13-step synthesis to the subunit is the aryl radical cyclization onto a vinyl chloride followed by resolution in a direct chromatographic separation. The determination of the biological activity in an in vitro assay shows that (IX) is highly potent and in the same range as the natural product duocarmycin SA. (IX) displays 7-50-fold higher potency than the unnatural (-)-enantiomer which is obtained analogously from (R)-(VIII). This is consistent with the biological findings of (+)-duocarmycin SA and its enantiomer. The tactical improvement defined in this work shortens approaches to related agents by 2-4 synthetic steps. This methodology should find application as a general synthetic approach to other member of this class of agents and related analogues. -(