Y-Pyrone moiety

Many of these possess complex structural frameworks and have been shown to exhibit interesting biological activities [5]. A common structural feature of this family of molecules is a y-pyrone moiety appended to an unsaturated, pol-yketide-derived side-chain. Tridachiahydropyrone (9) [6] and oxytridachiahydropyrone (10) [7] are unusual in possessing a dihydropyrone group, with the y-dihydropyrone fused to the side-chain, forming a bicychc core. 

In 2010, we achieved the first total synthesis of naturally occurring 2 [9]. Our synthetic plan is outlined in Scheme 8. The y-pyrone moiety present in 1 is considered to be an equivalent to vinylogous methyl ester therefore, the hydrolysis of this moiety followed by spmitaneous tautomerization to a-pyrone would form 2 via the plausible intermediates 34 and 35. To the best of our knowledge, the method for the conversion of 1 to 2 was hitherto unknown hence, this approach posed a cmisiderable challenge from the synthetic viewpoint. 

Initial attempts to realize the direct conversion of 1 to 2 under conventional basic conditions (1 M NaOH, MeOH, it reflux) were unsuccessful (Scheme 9). The expected hydrolysis of the y-pyrone moiety in 1 followed by the tautomerization of y-pyrone to a-pyrone proceeded smoothly and cleanly at reflux temperature however, the unfavorable deprotection of the acetyl group occurred during the reaction, producing de-O-acetylsesquicillin (37) in good yield (83%). Therefore, we decided to pursue the synthesis of 2 in a step-by-step manner from de-O-acetylnalanthalide (36), which is the most advanced intermediate of the nalanthalide synthesis (cf. Scheme 7, but... 

After obtaining the requisite intermediate 98, we then directed our attention to the synthesis of target 6 as shown in Scheme 22. The sequence involved the stereocontrolled formation of the tetrahydrofuran ring and subsequent conversion of the y-pyrone moiety into a-pyrone as the crucial steps. To this end, the removal of the TES protecting group from 98 followed by treatment with TsCl resulted in the formation of the desired cyclized product 99 in 80% overall yield as a single stereoisomer. We believe that the cyclized product 99 was formed from intermediate tosylate 88 (not isolated)... 

Scheme 22, 105 [103] 106 in Scheme 26), and (iv) conversion of the y-pyrone moiety into the corresponding a-pyrones (36 37 in Scheme 9, 99 6 in Scheme 22, 106 7 in Scheme 26). On the basis of the present study, we are currently synthesizing additional analogues of 1 and 3-7 with the aim of exploring their SARs. In addition, further investigations to identify the mechanism of action of 6 and 7 using the synthetic samples are in progress in our laboratories.

The structural elucidation of the secondary metabolites of Dictyosteiiium cellular slime molds was achieved by Y. Oshima et al. The total synthesis of a novel compound, dictyopyrone A, which possesses a unique a-pyrone moiety with a side-chain at the C3 position, was successfully carried out using the maionic ester synthesis. Meldrum s acid was acylated and the product was subjected to transesterification with an optically active did. Specific rotation of the final product was identical with that of the natural product, so the absolute configuration was established as (S). 

Rifamycin G [36] and 16,17-dehydrorifamycin G [37] are examples in the rifamycin series where C-1 is replaced by an oxygen atom. A y-pyrone ring is therefore present, instead of the quinone or dihydro-quinone moiety of other rifamycin type ansamycin anibiotics. 

In a continuation of our work on pinnatoxins, a novel marine alkaloid, pinnamine (10), was isolated from the Okinawan bivalve P. muricata. Pinnamine exhibited acute toxicity against mice, with characteristic toxic symptoms, such as scurrying around and convulsion (LD99 0.5 mg/kg) [17]. The structure of pinnamine (10) was determined to be a unique alkaloid containing a 9-azabicyclo[4.2.1]nonane moiety and a dihydro-y-pyrone ring. The absolute stereostructure was determined by an analysis of the circular dichroism spectrum [18]. 

The Simonis chromone synthesis is the reaction of a phenol la-c with a P-keto ester 2 using an appropriate acid promoter to generate a chromone or benzo-y-pyrone 3 (also called a benzo-l,4-pyrone). While compound 3 is actually a chromenone, for this article, whether the double bond is present or not, the system will be characterized as a chromone. The condensation is related to the Pechmann-Duisberg reaction, which yields coumarins from the condensation of a phenol with a P-keto ester and like its relative, the reaction conditions require the loss of water from the ketone moiety and alcohol from the ester moiety. 

The enantiorecognition of AurH was impressive, as illustrated by the preference of the enzymes to perform the C-H oxidation of primary carbons of (R)-22 rather than the secondary carbons of (S)-22, which was rather counterintuitive considering the general pattern of C-H oxidation (Scheme 34). Indeed, the oxidation at C9a seemed less favorable than the oxidation at C7 for electronic reasons, involving both the stabilization of radical species by the y-pyrone motif and the hydroxyl moiety. Oxidation at C7 led to ketone 27 as a short-lived intermediate en route to 2//-pyran 43 by a sequence of isomerization/electrocyclization. 

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