Polypropionate chains

Many examples of stereospecific allylation consistent with the above mechanism have been reported. As one example, the regioselective and highly diastereoselective allylation of the lactone 17 with the optically active allylic phosphate 16 proceeded with no appreciable racemization of the allylic part to give the lactones l8 and 19, and the reaction has been used for the synthesis of a polypropionate chain[26]. 

Polypropionate chains with alternating methyl and hydroxy substituents are structural elements of many natural products with a broad spectrum of biological activities (e.g. antibiotic, antitumor). The anti-anti stereotriad is symmetric but is the most elusive one. Harada and Oku described the synthesis and the chemical desymmetrization of meso-polypropionates [152]. More recently, the problem of enantiotopic group differentiation was solved by enzymatic transesterification. The synthesis of the acid moiety of the marine polypropionate dolabriferol (Figure 6.58a) and the elaboration of the C(19)-C(27) segment of the antibiotic rifamycin S (Figure 6.58b) involved desymmetrization of meso-polypropionates [153,154]. 

During the course of the development of our group s alkylation/reductive decyanation strategy, a very reliable method for distinguishing between syn-and anfz-l,3-diols was discovered [17,18]. The acetonide methyl groups reliably display diagnostic C-NMR chemical shifts, allowing for stereochemistry to be determined simply by inspection (Fig. 1). Evans later extended the C-NMR chemical correlation to polypropionate chains [19,20]. 

An interesting pericyclic-anionic-pericyclic domino reaction showing a high stereoselectivity is the cycloaddition-aldol-retro-ene process depicted in scheme 20.1581 The procedure presumably starts with a [4+2]-cycloaddition of diene 98 and S02 in presence of a Lewis acid. After opening of the formed adduct reaction with (Z)-silyl vinyl ether 99 leads to a mixture of alk-2-enesulfinic acids 101. It follows a retro-ene reaction which affords a 7 3 mixture of the products 102 and 103. The reaction described by Vogel et al is a nice example for the efficient generation of polypropionate chains with the stereoselective formation of three stereogenic centers and one (0-double bond in a three-component domino reaction in its strict definition. 

In 1997 (-)-callystatin A (Fig. 1.2.2), a potent cytotoxic polyketide, was isolated from the marine sponge Callyspongia truncata and structurally elucidated by Ko-bayashi et al. [20] shortly afterward its absolute configuration was confirmed by the same authors by total synthesis [21]. The structure of (-)-callystatin A shows a polypropionate chain and a lactone ring connected to each other by two diene systems separated by two sp carbon atoms (Fig. 1.2.2). Since this arrangement is structurally related to several antitumor antibiotics and due to the fact that only very small amounts can be isolated from natural sources, callistatin A has been... 

Furthermore, the authors explored the epoxidation of more complex homoallylic alcohols, in view of their application as precursors for the synthesis of the polypropionate chains of Streptovaricins D and U (Scheme 45) [ 187— 189]. These complex alcohols were found to undergo the VO(acac)2-catalyzed epoxidations smoothly under microwave-assisted conditions and the products were isolated in very high yields in only 10 min, after being protected as the corresponding acetonides (Scheme 45). Moreover, in this specific case, the authors were successful in obtaining exclusive diastereoselectivity, as only the sjn-isomers were isolated as the products of epoxidation. 

Allylations. Double stereodifferentiation in the crotylation of aldehydes permits the construction of polypropionate chain segments of natural products. The diastereoselection and absolute stereochemistry are determined by the local chiralities of the two components. 

Lewis acidity L Other notable additions to the chiral pool include chiral bicyclic lactams and further chiral sultam derivs., while syntheses with chiral acyl carbanion equivalents, silanes N-acyl-immonium salts and pyran templates are of obvious application, the last-mentioned being adaptable for a reiterative generation of the key polypropionate chain of macrolide antibiotics. Asym. syntheses via organometallics have also been succinctly reviewed" ... 

The high regio- and diastereoselectivity to be gained from aluminum-chelated transition states was demonstrated with a repetitive synthesis of a polypropionate chain [24]. 

The racemic enone (24) has been made as indicated in Scheme 7 and used in the synthesis of the polypropionate chain of Rifaroycin S (Chapter 24). ... 

Polypropionate chains can be described and their synthesis can be planned in terms of stereotriads, stereotetrads, stereopentads, and so on. The term stereo-tri-ad or in a broader sense the concept of stereo- -ad was introduced by R. W. Hoffmann and has become accepted within the scientific community. " Thus, the family of stereo-triads possesses 8 members, stereotetrads are accordingly... 

The naked sugar approach, developed and successfully applied by Vogel and co-workers for the synthesis of many natural products, was applied also for the synthesis of polypropionate chains. Thus, the Diels-Alder reaction between 2,4-dimethylfuran 261 and enantiomerically pure... 

Also, [4 + 3] cycloaddition employing furan derivatives can be used to construct polypropionate chains. Thus,... 

Carretero JC, Dominguez E. A new method for the iterative construction of enantiomerically pure polypropionate chains. J. Org. Chem. 1993 58(6) 1596-1600. 

Dominguez E, Carretero JC. Flexible and stereoselective construction of polypropionate chains from enantiomerically pure "y-hydroxy-a,P-unsaturated sulfones. Tetrahedron 1994 50(25) 7557-7566. 

Hayakawa, H. and Miyashita, M. (1999) A tandem synthesis of polypropionate chains. Highly stereoselective construction of the C (13)-C(25) segment containing nine contiguous chiral centers of swinholides A—C based on the stereospedfrc methylation of y,6-epoxyacrylates by trimefhylaluminium. J. Chem. Soc. Perkin Trans. I. 3399-3401. 

---