Total Synthesis, Structural Revision, and Absolute Configuration of (+)-Clavosolide A

Son, Jung Beom; Kim, Si Nae; Kim, Na Yeong; Lee, Duck‐Hyung

doi:10.1021/ol052851n

Cited by 51 publications

(30 citation statements)

References 33 publications

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“…Structural motifs misassigned on the basis of NOEs include epoxides (calafianin, 96–98 symbiodinolide 99, 100 ), cyclopropyl rings (clavosolide A, 101, 102 laurentristich-4-ol 103, 104 ), bridges (vannusals A and B 105–107 ), fused ring junctions (itomanallene A, 108, 109 asperdimin, 110, 111 aplysiallene 112, 113 ), polyethers (aplysiol B, 114, 115 azaspiracids 116–119 ), vicinal polyols (amphidinolide H2, 120, 121 hyrtiosterol, 122, 123 pericosine A 124, 125 ), sugars (callipeltoside C; 126, 127 fusapyrone and deoxyfusapyrone, 128, 129 Table 6) and macrolides (palmerolide A, 130–132 neopeltolide 133, 134 ).…”

Section: Sources Of Natural Product Structural Misassignmentsmentioning

confidence: 99%

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

Suyama

Gerwick

McPhail

2011

Bioorganic & Medicinal Chemistry

164

175

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The structural assignment of new natural product molecules supports research in a multitude of disciplines that may lead to new therapeutic agents and or new understanding of disease biology. However, reports of numerous structural revisions, even of recently elucidated natural products, inspired the present survey of techniques used in structural misassignments and subsequent revisions in the context of constitutional or configurational errors. Given the comparatively recent development of marine natural products chemistry, coincident with the modern spectroscopy, it is of interest to consider the relative roles of spectroscopy and chemical synthesis in the structure elucidation and revision of those marine natural products which were initially misassigned. Thus, a tabulated review of all marine natural product structural revisions from 2005 to 2010 is organized according to structural motif revised. Misassignments of constitution are more frequent than perhaps anticipated by reliance on HMBC and other advanced NMR experiments, especially considering the full complement of all natural products. However, these techniques also feature prominently in structural revisions, specifically of marine natural products. Nevertheless, as is the case for revision of relative and absolute configuration, total synthesis is a proven partner for marine, as well as terrestrial, natural products structure elucidation. It also becomes apparent that considerable ‘detective work’ remains in structure elucidation, in spite of the spectacular advances in spectroscopic techniques.

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Section: Sources Of Natural Product Structural Misassignmentsmentioning

confidence: 99%

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

Suyama

Gerwick

McPhail

2011

Bioorganic & Medicinal Chemistry

164

175

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“…Literature precedent for the synthesis of (−)‐clavosolide A and (−)‐cyanolide A indicated that the glycosylation of the symmetrical parent diol of a bis‐macrolactone precursor led to a statistical mixture of [ α,α ]‐, [ β,β ]‐, and [ α,β ]‐anomers, which reduced the overall yield of the total synthesis . Thus, in designing the synthetic strategy to cocosolide we aimed to close the macrocycle via the dimerization of the permethylated‐ d ‐xylose‐containing monomer 21 , which could be obtained from glycosylation of alcohol 19 .…”

Section: Resultsmentioning

confidence: 99%

Discovery, Total Synthesis and Key Structural Elements for the Immunosuppressive Activity of Cocosolide, a Symmetrical Glycosylated Macrolide Dimer from Marine Cyanobacteria

Gunasekera

Ratnayake

et al. 2016

Chemistry A European J

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A new dimeric macrolide xylopyranoside, cocosolide (1), was isolated from the marine cyanobacterium preliminarily identified as Symploca sp. from Guam. The structure was determined by a combination of NMR, HRMS, X-ray diffraction studies and Mosher’s analysis of the base hydrolysis product. Its carbon skeleton closely resembles that of clavosolides A–D isolated from the sponge Myriastra clavosa, for which no bioactivity is known. We performed the first total synthesis of cocosolide (1) along with its [α,α]-anomer (26) and macrocyclic core (28), thus leading to the confirmation of the structure of natural 1. The convergent synthesis featured Wadsworth–Emmons cyclopropanation, Sakurai annulation, Yamaguchi macrocyclization/dimerization reaction, α-selective glycosidation and β-selective glycosidation. Compounds 1 and 26 potently inhibited IL-2 production in both T-cell receptor dependent and independent manners. Full activity requires the presence of the sugar moiety as well as the intact dimeric structure. Cocosolide (1) also suppressed the proliferation of anti-CD3-stimulated T-cells in a dose-dependent manner.

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“…This methodology has been applied to the total synthesis of several natural polyketides, including leucascandrolide A [52], clavosolide A [53], peloruside A [54], dolabelide D [55], and oasomycin A [56].…”

Section: ) [48]mentioning

confidence: 99%

Asymmetric Induction in Aldol Additions

Dias¹,

Polo²,

Lucca³

et al. 2013

Modern Methods in Stereoselective Aldol Reactions

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The selectivity of aldol reactions involving kinetic enolates is related to various factors such as the nature of the Lewis acid (Li, Mg, B, Al, Ti, Sn, etc.), the presence of stereogenic centers in both the substrates and reagents, the nature of their substituents and the reaction conditions. Another factor of major importance is the nature of the enolate double bond (Z or E) [1].In general, it is well known that in aldol reactions involving metal enolates, which proceed through a six-membered cyclic transition state, the Z-enolate leads to the formation of 1,2-syn aldol adducts and the E-enolate affords aldol adducts with the 1,2-anti configuration. A rationalization for the observed selectivities of these aldol reactions was proposed by Zimmerman and Traxler (Scheme 5.1) [2]. According to this model, the nature of the double bond geometry plays a primary role in determining the energies of the competing transition states. For Z-enolates, the transition state TS2 is more destabilized than transition state TS1 because of the 1,3-diaxial interactions between the R 1 and R 3 substituents as well as between these substituents and one of the metal ligands (L). Therefore, the Z-enolate preferentially leads to the formation of the 1,2-syn aldol adduct.For the E-enolate, 1,3-diaxial interactions between the R 1 and R 3 substituents and between both R 1 and R 3 and one of the metal ligands are present in transition state TS4. Therefore, the 1,2-anti aldol adduct is obtained from the lower energy transition state TS3.Modern aldol reactions use preformed enolates to obtain good yields by preventing side reactions. This methodology has proven to be very effective for various Lewis acids derived from lithium, titanium, tin, and boron. By using preformed enolates with chiral substrates and reagents, it is possible to obtain aldol adducts with an excellent degree of asymmetric induction.The IUPAC defines asymmetric induction as the traditional term describing the preferential formation in a chemical reaction of one enantiomer (or diastereomer) over the other as a result of a chiral feature present in the substrate, reagent, catalyst, or the environment [3].

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Total Synthesis, Structural Revision, and Absolute Configuration of (+)-Clavosolide A

Cited by 51 publications

References 33 publications

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

Discovery, Total Synthesis and Key Structural Elements for the Immunosuppressive Activity of Cocosolide, a Symmetrical Glycosylated Macrolide Dimer from Marine Cyanobacteria

Asymmetric Induction in Aldol Additions

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