Polypropionate structures

Allyl epoxides are produced by the acclaimed Sharpless asymmetric epoxidation reaction [75], and are important intermediates and products. For example, an allyl epoxide is a vital part of the structure of amphidinolides, a series of unique macrolides isolated from dinoflagellates (Amphidinium sp.). Amphidinolide H (AmpH) is a potent cytotoxic 26-membered macrolide with potent cytotoxicity for several carcinoma cell lines [76]. An allyl epoxide is involved in the total synthesis of prostaglandin A2 with a cuprate reagent [77]. Allyl epoxides derived from Sharpless chemistry are a practical method for construction of polypropionate structures by Lewis acid-induced rearrangement [78,79]. Other allyl epoxides such as l,2-epoxy-3-methyl-3-butanol are useful organic intermediates for the production of a-hydroxyketones, which are used for the synthesis of various natural... 

This review deals with recent advances in the synthesis of polypropionate structures. It focuses on the total synthesis of natural products (citreoviral, ACRL toxin IECB) as well as on new synthetic methodology (chiral methyl branching, base induced 1,3-H-shift and chiral methyl groups). 

The combination of NMR spectroscopy and X-ray crystallographic analysis revealed a novel polypropionate structure for discodermolide (104) [114], a polyhydroxylated lactone isolated from Discodermia... 

Stereoselective addition of cuprates to ji-alkoxy enoates of type 49 [17] isee Sdiemes 6.8 and 6.9) bas been used in die crrnstruction of polypropionate-type structures. Tlius, a sequence of diastereoselective cuprate addition, etiolate for-ruabon, and diastereoselective oxygenation widi Davis s reagent bas been applied iteratively to provide a Cio segment of Rifaruycin S i60) [ 17c, d]. 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

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]. 

Tridachiahydropyrone belongs to the family of marine polypropionates [69]. Efforts towards its total synthesis have recently led to a revision of the structure with the new proposal 2-147 [70]. The construction of the highly substituted cyclohex-enone moiety 2-146 which could be incorporated into this natural product [71] has been described by Perkins and coworkers (Scheme 2.33) [70, 72]. The conjugate addition/ Dieckmann-type cydization utilizing organocopper species as Michael donors afforded the enantiopure 2-145 in 68% yield. A further methylation of the (3-ketoester moiety in 2-145 followed by an elimination led to the desired cydohex-enone 2-146. 

B. striata, its secondary metabolic pattern, consisting of a series of uncommon polypropionates, is almost identical to that of its prey [36,37], On the contrary, if the mollusc, under maintenance in an aquarium, feeds on Haminoea navicula, it discharges [5] in the form of a yellow secretion two Haminoea metabolites, the haminols (8,9), structurally related to navenone-A (I), which possess alarm pheromone properties [38] for H. navicula. Studies on a third Aglajidae mollusc [39, 40], Philinopsis speciosa, led to the characterization of a 2-alkyl-pyridine, pulo upone (10), as a minor constituent co-occurring with two polypropionates closely related to the metabolites from the pair P. depicta-B. striata. 

Although the epothilones are structurally less complex that the taxanes, we foresaw several synthetic issues concerning this venture that would require careful attention. The structures of the epothilones invite retrosynthetic dissection into two regions. The polypropionate domain of the epothilones constitutes carbons C1-C8, while the... 

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... 

Suenaga, K., Kigoshi, H., and Yamada, K., Auripyrones A and B, cytotoxic polypropionates from the sea hare Dolabella auricularia isolation and structures, Tetrahedron Lett., 39, 5151, 1996. 

A chemical study of an acetone extract of the Mexican, maura (collected at Sayulita, Mexico) resulted in the isolation of two polypropionate metabolites, vallartanone A [ 15 5] and vallartanone B [156](114) which have structures quite different from other polypropionate metabolites of the genus Siphonaria. An unrelated polypropionate, maurenone [150] which was previously isolated from the Mexican 5. maura was also present along with vallartanone A and B. It appears that pulmonates of the genus Siphonaria synthesize similar metabolites derived fiom the condensation... 

In addition to siphonarin A [140], the fljian mollusk Siphonaria normalis has been reported to contain an unusual tricyclic ketal with a trioxaadamantane ring skeleton. The structure of muamvatin 2 [161] was determined by nmr spectroscopy (118). The possible roles of the polypropionate metabolites isolated from S honaria species could be associated with its trailfollowing habits along with defense against predators. 

Structurally, (+)-DDM 1 comprises a linear polypropionate backbone, punctuated by 13 stereogenic centers, Z-olefinic linkages at C8-C9 and C13-C14, a terminal Z-diene substituent at C21-C24, a carbamate function, and a 8-lactone (Figure 1). 

In recent years, a number of structurally diverse y-pyrone-containing polypropionate natural products have been isolated from opisthobranch molluscs of the order Sacoglossa (Fig. 1.1) [1 ]. 

Spongistatins 113, also referred to as altohyrtins in the literature, are complex marine macrolides that were isolated from marine sponges (Figure 19.10) [60]. Aside from the formidable structure, interest in these compounds has been stimulated due to their potent antitumor activity. Schwenter and Vogel, who have developed a new methodology for the preparation of polypropionates based on a double [4+3] cycloaddition, saw the spongistatins as an opportunity to... 

This chapter will deal mainly with polypropionate fragments, the structures of which are built of an aliphatic chain substituted alternately with methyl and hydroxyl groups. On the other hand, chemical syntheses of reduced polypropionates or deoxypropionates are reported and have recently been reviewed. ... 

On the contrary, Panek et al. s crotylsUanes of type 227 containing asymmetric carbon chain have been used with good success in the construction of polypropionates. Their structures have been elegantly incorporated into the... 

Dolabriferol was isolated from Dolabrifera dolabrifera, a shell-less mollusk. This natural product is made of two polypropionate subunits linked by an ester function, a structural motif that is also found in baconipyrones A-D (see section 4.3). Dolabriferol is assumed to protect the mollusk from predators. When the Vogel s cascade... 

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