Synthesis of Polyketides

These mesylates, in turn, can be converted to enantioenriched allenyltin, zinc, and indium reagents which add to aldehydes with excellent diastereo-and enantioselectivity to afford either syn- or anti-homopropargylic alcohols or allenylcarbinols (eq 2, 3, and 4).3 4 Adducts of this type serve as useful intermediates for the synthesis of polyketide and hydrofuran natural products.5... 

These reagents exhibit reagent control of stereoselectivity and have proven to be very useful in stereoselective synthesis of polyketide natural products, which frequently contain arrays of alternating methyl and oxygen substituents.44... 

Leighton and coworkers [217] have also used this approach to develop efficient strategies for the synthesis of polyketide-derived natural products [218]. A main motif of these compounds is a skipped polyol structure, as in 6/2-94 this can easily be prepared by a novel Rh-catalyzed domino reaction of a diallylsilyl ether in the presence of CO, followed by a Tamao oxidation [219]. Thus, reaction of, for example, the silane 6/2-93, which is readily prepared from the corresponding ho-... 

In a synthesis of polyketides, Kocienski crafted indole 78 from 2-iodo-l-methylindole and the appropriate organozinc reagent 77 derived from the corresponding stannane (76), which itself was reluctant to undergo a Stille coupling [106],... 

A carbohydrate based approach to the synthesis of polyketide acid unit present in nagahamide A has been reported. Reductive transformation of 183 followed by cyclization allowed to prepare 184 (Fig. 58).75... 

Additions of enantioenriched allenylzinc reagents to chiral aldehydes provide intermediates that can be employed in the synthesis of polyketide natural products. Matched and mismatched pairing of reagent and substrate can result in enhanced or diminished diastereoselectivity (Eqs. 9.132 and 9.133) [114]. 

The power of this methodology is demonstrated with the synthesis of polyketide-like structures by repetitive application of the same procedure (Scheme 22) [76]. 

Scheme 1 Comparison of biosynthesis and laboratory synthesis of polyketide fragments...

Aldehyde 11a, produced by diastereoselective hydroformylation (R=Me Scheme 5.4), has been employed in the synthesis of polyketide fragment 40, a key building block for the synthesis of bafilomycin Ai (Scheme 5.16) [21]. 

R Pieper, G Luo, DE Cane, C Khosla. Cell-free synthesis of polyketides by recombinant erythromycin polyketide synthases. Nature 378 263-266, 1995. 

I. Paterson C. J. Cowden, D. J. Wallace, Stereoselektive Aldol Reactions in the Synthesis of Polyketide Natural Products, in Modem Carbonyl Chemistry, Ed. J. Otera, Wiley-VCH, Weinheim, 2000, 249-297. 

Oikawa, Y, Nishi, T, Yonemitsu, O, Chiral synthesis of polyketide-derived natural product. Chemical correlation of chiral synthons, derived from D-glucose for the synthesis of erythromycin A, with chemical cleavage products of the natural antibiotic, J. Chem. Soc., Perkin. Trans. 1, 27-33, 1985. 

Hikota, M., Tone, H., Horita, K., Yonemitsu, O. Chiral synthesis of polyketide-derived natural products. 31. Stereoselective synthesis of erythronolide A by extremely efficient lactonization based on conformational adjustment and high activation of seco-acid. Tetrahedron 1990, 46, 4613 628. 

Stereoselective Aldol Reactions in the Synthesis of Polyketide Natural Products... 

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