Total Synthesis of the Marine Natural Product (−)-Clavosolide A

Cs, Barry; Elsworth, J. D.; Seden, PT; Bushby, Nick; Harding,; Alder, Roger W.; Willis, Chris

doi:10.1021/ol0611705

Cited by 59 publications

(32 citation statements)

References 21 publications

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“…They share a flat dimeric macrocyclic skeleton that is decorated with xylose appendages, the same configuration for their analogous stereocenters throughout the entire molecule, and negative specific rotation values of approximately the same magnitude (Table S3, Supporting Information). The triacetylated xylose residues possess virtually identical 1 H and 13 C chemical shifts (Tables S1 and S2, Figure S7), which in the case of clavosolides A ( 3 ),17 B ( 4 )18 and D ( 6 ),19 have been found to have the D-configuration via total synthesis. However, cyanolide A ( 2 ) lacks the trans -2-methylcyclopropyl substituents at the C-9/C-9′ position of the clavosolides, instead possessing an ethyl group.…”

mentioning

confidence: 99%

Cyanolide A, a Glycosidic Macrolide with Potent Molluscicidal Activity from the Papua New Guinea Cyanobacterium Lyngbya bouillonii

2010

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confidence: 99%

Cyanolide A, a Glycosidic Macrolide with Potent Molluscicidal Activity from the Papua New Guinea Cyanobacterium Lyngbya bouillonii

2010

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“…DIBAL reduction of 5 and a second Brown allylation led to a homoallylic secondary alcohol product, from which a second b-alkoxyacrylate derivative 6 was obtained by reaction with methyl propiolate. In the presence of trifluoroacetic acid, Prins cyclization [2] of 6 was successful and the products were hydrolyzed to a mixture ( % 3:1) of alcohols, which was then converted into the ketone derivative 7 by Dess-Martin oxidation. There were signs of partial ( % 7:1) racemization [7] in the Prins cyclization step.…”

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confidence: 99%

Total Synthesis of (+)‐Exiguolide

Kwon

Woo

et al. 2008

Angew Chem Int Ed

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Exiguolide (1) is a unique 16-membered macrolide isolated from the marine sponge Geodia exigua Thiele (order Astrophorida, family Geodiidae).[1] It specifically inhibits fertilization of sea urchin (Hemicentrotus pulcherrimus) gametes but not embryogenesis of the fertilized egg. The macrolide structure incorporates two cis-2,6-disubstituted oxane rings, one of which carries an exocyclic enoate appendage reminiscent of bryostatins. The unique structural features and interesting biological activity of 1 has generated considerable interest in this compound, and herein we report our recent results for the total synthesis of 1.Scheme 1 shows the retrosynthetic analysis of 1. Thus, the target would be synthesized through a ring-closing olefin metathesis reaction of the carboxylate ester A followed by construction of the triene side chain. Fragments B and C are the constituents of the ester A. Fragment B may be obtained from Prins cyclization [2] of the b-alkoxyacrylate D, which should be accessible from the oxane derivative E. Fragment E may in turn be obtained by radical cyclization [3] of the b-alkoxyacrylate F.For synthesis of the B fragment, the secondary alcohol 3 was prepared from the known aldehyde 2[4] through Brown allylation, [5] hydroboration-oxidation, and protection of the primary hydroxy group with TBS (Scheme 2). The reaction of 3 with methyl propiolate in the presence of N-methylmorpholine produced the corresponding b-alkoxyacrylate derivative, which was converted into the iodide 4 by cleavage of the TBS group and iodide substitution. Radical cyclization [3] of 4 in the presence of 1-ethylpiperidinium hypophosphite and triethylborane in ethanol [6] proceeded efficiently and selectively to yield, almost quantitatively, the oxane 5. DIBAL reduction of 5 and a second Brown allylation led to a homoallylic secondary alcohol product, from which a second b-alkoxyacrylate derivative 6 was obtained by reaction with methyl propiolate. In the presence of trifluoroacetic acid, Prins cyclization [2] of 6 was successful and the products were hydrolyzed to a mixture ( % 3:1) of alcohols, which was then converted into the ketone derivative 7 by Dess-Martin oxidation. There were signs of partial ( % 7:1) racemization [7] in the Prins cyclization step. The keto ester 7 was converted into the keto acid 8 by dimethyl ketalization-hydrogenolysis, Dess-Martin oxidation, and rhodium-catalyzed methylenation [8] of the product aldehyde, followed by hydrolysisdeketalization and subsequent chromatographic separation.The known aldehyde 9 [9] served as the starting material in the synthesis of the C fragment (Scheme 3). Brown crotylation [10] of 9 produced the allylic alcohol 10, but a Sharpless kinetic resolution [11] step had to be included for improvement of the enantiomeric purity. For preparation of the final Scheme 1. Retrosynthetic analysis of exiguolide (1).

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“…Following our reports on the structure of the revised clavosolde A (5), Smith,37 Willis, 38 and Chakraborty 39 unambiguously determined the absolute stereochemistry of (-)-clavosolide A as (5) by comparison of the optical rotation values.…”

Section: Synthesis Of Revised Clavosolide a (5)mentioning

confidence: 77%

“…8 Willis also proposed a revised structure 5 for the natural clavosolide A 5 and our group confirmed the relative stereochemistry of clavosolide A (5) by stereoselective total synthesis ( Figure 2). 8a Subsequently, Smith,9 Willis, 10 and Chakraborty 11 unambiguously determined the absolute stereochemistry of (-)-clavosolide A (5) by comparison of the optical rotation.…”

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Enantioselective Total Synthesis of (-)-Clavosolide A and B

Son¹,

Kim²,

Kim³

et al. 2010

Bulletin of the Korean Chemical Society

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Enantioselective total synthesis of (-)-clavosolide A and B was reported in full including the synthesis of proposed structure of (-)-clavosoldie A (1), revised structure of (-)-clavosoldie A (5), and revised structure of (-)-clavosoldie B (6). The relative and absolute stereochemistries of the natural products were confirmed unambiguously by comparing the optical rotation values and 1 H and 13 C NMR spectra of them.

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Total Synthesis of the Marine Natural Product (−)-Clavosolide A

Abstract: [Structure: see text] The total synthesis of the marine metabolite clavosolide A is reported which confirms the structure and absolute configuration of the natural product as the symmetrical diolide glycosylated by permethylated D-xylose moieties, 2.

Cited by 59 publications

References 21 publications

Cyanolide A, a Glycosidic Macrolide with Potent Molluscicidal Activity from the Papua New Guinea Cyanobacterium Lyngbya bouillonii

Cyanolide A, a Glycosidic Macrolide with Potent Molluscicidal Activity from the Papua New Guinea Cyanobacterium Lyngbya bouillonii

Total Synthesis of (+)‐Exiguolide

Enantioselective Total Synthesis of (-)-Clavosolide A and B

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