195377-47-0Relevant articles and documents
A general and stereocontrolled strategy for the iterative assembly of enantiopure polypropionate subunits: Synthesis of the C19-C28 segment of rifamycin S from a single chiron
Hanessian, Stephen,Wang, Wengui,Gai, Yonghua,Olivier, Eric
, p. 10034 - 10041 (2007/10/03)
An operationally simple method has been developed for the stereocontrolled construction of polypropionate stereotriads in high enantio- and diastereomeric purities. The method consists of the stereocontrolled addition of lithium dimethylcuprate to an enantiopure γ-alkoxy-α,β-unsaturated ester, followed by hydroxylation of the corresponding enolate. This leads to an anti/syn orientation of the γ-alkoxy-β-methyl-α-hydroxy ester unit. Chain extension and reiteration of the process, after appropriate functionalization, lead ultimately to an 11-carbon acyclic chain harboring three contiguous polypropionate triads with the correct anticipated absolute configuration. The method relies on two basic bond-forming reactions that involve consecutive 1,2-induction. It is admirably stereocontrolled through four iterative cycles of cuprate additions and hydroxylations. Inversion of the α-alkoxy group after each α-hydroxylation allows passage to stereotriads of different configurations. Thus three of the four possible stereotriad combinations are accessible directly using this simple and general method. The C19-C28 acyclic chain of rifamycin S. harborng eight stereogenic carbon atoms (three triads), was constructed starting with an enantiopure precursor that contains a single stereogenic center. A common precursor serves as:the starting chiron for a variety of other propionate derived macrolides and ionophores.
