Synthesis of the 5-hydroxymethyl-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one natural products descurainin and cartorimine

Snider, Barry B.; Grabowski, James F.

doi:10.1016/j.tet.2005.10.083

Cited by 33 publications

(20 citation statements)

References 19 publications

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“…Acetoxy pyrones 4a-c were prepared from corresponding furyl alcohols 9 or fructose. 10 Enamides 5a, 5f and 5g were prepared via palladium catalysed trans-vinylations; 11 ynamide 5e and enamides 5b-d and 5h were prepared by copper catalysed cross-couplings. 12 At first we decided to establish the best cycloaddition conditions for reactions with non-chiral enamides (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Diastereoselective 1,3-dipolar cycloaddition of pyrylium ylides with chiral enamides

et al. 2012

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Section: Resultsmentioning

confidence: 99%

Diastereoselective 1,3-dipolar cycloaddition of pyrylium ylides with chiral enamides

et al. 2012

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“…In this context, it is interesting that Snider and Grabowski recently proposed in their total syntheses of (±)‐cartorimine and (±)‐descurainin that the 8‐oxabicyclo[3.2.1]octenone skeleton of these molecules would be biosynthesized by a [5+2] cycloaddition between a oxypyrylium zwitterion and an alkene 5e. f They speculated that [5+2] cycloadditions in a chiral environment could lead to optically enriched products as the very small [ α ] D values of these natural products indicate that they are not completely racemic. We surmise that polygalolides would also be synthesized in the medicinal plant through [5+2] cycloaddition of the fructose‐derived oxypyrylium zwitterion 25 with an isoprene derivative, followed by an intramolecular hetero‐Michael addition, a lactone formation, and an aldol reaction with vanillin derivatives 18.…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis and Absolute Stereochemistry of Polygalolides A and B

Nakamura¹,

Sugano²,

Kikuchi³

et al. 2006

Angew Chem Int Ed

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In 2003, Wei and co-workers reported the isolation and structural elucidation of the polygalolides A (1) and B (2) obtained from Polygala fallax Hemsl., a medicinal plant from which extracts are used as tonics and antihepatitis drugs in China.[1] The structure and relative configuration of the polygalolides were determined on the basis of NMR spectroscopic data. However, the issue of the absolute stereochemistry of the molecules has not been resolved. The structural complexity of these molecules, which include an unprecedented trioxatetracyclic ring system and contiguous quaternary stereogenic centers at C2 and C8, poses a considerable synthetic challenge. Herein, we describe the first total synthesis of (À)-polygalolides A (1) and B (2). The synthesis takes advantage of a transformation consisting of a tandem carbonyl ylide formation/1,3-dipolar cycloaddition, which has been extensively studied, especially in the research group of Padwa. [2][3][4][5] Our retrosynthetic analysis of the polygalolides is illustrated in Scheme 1. We elected to introduce the arylmethylidene moiety at a late stage in the synthesis, and the scission of the lactone ring provided 3 as a common intermediate. The tricyclic compound 3 was assumed to arise from an intramolecular 1,3-dipolar cycloaddition of carbonyl ylide 5, generated from a-diazoketone 6 in the presence of a Rh II catalyst. Compound 6 arises from homologation of the tert-butyl ester 7, which would be elaborated from the known alcohol 8, [6] which in turn can readily be obtained from d-arabinose.We initiated the synthesis by alkylating alcohol 8 with (Z)-1-bromo-4-(tert-butyldiphenylsilyl)oxy-2-butene [7] to provide the allyl ether 9 in 98 % yield (Scheme 2). The oxidative hydrolysis of the dithioacetal with iodine was followed by oxidation with NaClO 2 and esterification with (Boc) 2 O[8] to give tert-butyl ester 10 in 70 % yield over three steps. Catalytic hydrogenation of alkene 10 provided the TBDPS ether 11 in 95 % yield, and 11 was then treated with Bu 4 NF in the presence of AcOH to give alcohol 12 in 96 % yield. Installation of the C2=C3 bond was accomplished by employing a modification of the procedure reported by Ogasawara and co-workers, [9] and subsequent reduction with NaBH 4 gave alcohol 13 in 81 % yield over both steps. A two-step sequence involving mesylation and nucleophilic substitution with pmethoxyphenol was used to convert the allyl alcohol 13 into the PMP ether 14 in 78 % overall yield. The acetonide was Scheme 1. Retrosynthetic analysis of polygalolides A and B. PMP = p-methoxyphenyl, TBDPS = tert-butyldiphenylsilyl.

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“…Notably, 100 mol% of triethylamine gave the highest yield and the productivity of 3 a dropped not only under 200 mol% but also under 20 mol% conditions (Figure b). These results suggest that excess base is not necessarily good for this type of transformation, which might have caused the low yields of cycloadducts in the previous reports ,. Most importantly, introduction of a Boc group enabled the organic base to convert substrates to products in catalytic fashion.…”

Section: Methodsmentioning

confidence: 79%

Triethylamine Enables Catalytic Generation of Oxidopyrylium Ylides for [5+2] Cycloadditions with Alkenes: An Efficient Entry to 8‐Oxabicyclo[3.2.1]octane Frameworks

et al. 2018

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Synthesis of the 5-hydroxymethyl-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one natural products descurainin and cartorimine

Cited by 33 publications

References 19 publications

Diastereoselective 1,3-dipolar cycloaddition of pyrylium ylides with chiral enamides

Diastereoselective 1,3-dipolar cycloaddition of pyrylium ylides with chiral enamides

Total Synthesis and Absolute Stereochemistry of Polygalolides A and B

Triethylamine Enables Catalytic Generation of Oxidopyrylium Ylides for [5+2] Cycloadditions with Alkenes: An Efficient Entry to 8‐Oxabicyclo[3.2.1]octane Frameworks

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