Formal Synthesis of Natural 1,3‐Polyol/<i>α</i>‐Pyrone Diastereoisomers

Sabitha, Gowravaram; Gopal, Peddabuddi; Yadav, J. S.

doi:10.1002/hlca.200890243

Cited by 7 publications

(1 citation statement)

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“…Thus, starting from phenyl hexanal 5 and using d -proline as a catalyst, all three stereogenic centers were generated in an iterative fashion following a similar sequence of reaction as described above to give 14 which was eventually converted into 15 via ring closing metathesis. Since the monoacetylation of lactone 15 to the target molecules has already been reported, this constitutes the formal synthesis of 16a and 16b (Scheme ).…”

Section: Applicationsmentioning

confidence: 99%

Proline Catalyzed α-Aminoxylation Reaction in the Synthesis of Biologically Active Compounds

Kumar

Dwivedi

2012

Acc. Chem. Res.

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The search for new and efficient ways to synthesize optically pure compounds is an active area of research in organic synthesis. Asymmetric catalysis provides a practical, cost-effective, and efficient method to create a variety of complex natural products containing multiple stereocenters. In recent years, chemists have become more interested in using small organic molecules to catalyze organic reactions. As a result, organocatalysis has emerged both as a promising strategy and as an alternative to catalysis with expensive proteins or toxic metals. One of the most successful and widely studied secondary amine-based organocatalysts is proline. This small molecule can catalyze numerous reactions such as the aldol, Mannich, Michael addition, Robinson annulation, Diels-Alder, α-functionalization, α-amination, and α-aminoxylation reactions. Catalytic and enantioselective α-oxygenation of carbonyl compounds is an important reaction to access a variety of useful building blocks for bioactive molecules. Proline catalyzed α-aminoxylation using nitrosobenzene as oxygen source, followed by in situ reduction, gives enantiomerically pure 1,2-diol. This molecule can then undergo a variety of organic reactions. In addition, proline organocatalysis provides access to an assortment of biologically active natural products including mevinoline (a cholesterol lowering drug), tetrahydrolipstatin (an antiobesity drug), R(+)-α-lipoic acid, and bovidic acid. In this Account, we present an iterative organocatalytic approach to synthesize both syn- and anti-1,3-polyols, both enantio- and stereoselectively. This method is primarily based on proline-catalyzed sequential α-aminoxylation and Horner-Wadsworth-Emmons (HWE) olefination of aldehyde to give a γ-hydroxy ester. In addition, we briefly illustrate the broad application of our recently developed strategy for 1,3-polyols, which serve as valuable, enantiopure building blocks for polyketides and other structurally diverse and complex natural products. Other research groups have also applied similar strategies to prepare such bioactive molecules as littoralisone, brasoside and (+)-cytotrienin A. Among the various synthetic approaches reported for 1,3-polyols, our organocatalytic iterative approach appears to be very promising and robust. This method combines the merit of organocatalytic reaction with an easy access to both enantiomerically pure forms of proline, mild reaction conditions, and tolerance to both air and moisture. In this Account, we present the latest applications of organocatalysis and how organic chemists can use this new tool for the total synthesis of complex natural products.

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Section: Applicationsmentioning

confidence: 99%