Stereoselective synthesis of two stereoisomers of demethylgorgosterol

Anderson, Gary D.; Powers, T.J.; Djerassi, Carl; Fayos, J.; Clardy, Jon

doi:10.1021/ja00835a029

Cited by 38 publications

(19 citation statements)

References 11 publications

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“…The first two steps were necessary to protect the steroidal A‐ and B‐rings in the form of the i ‐steroid methyl ether 16 [25] . This was followed by the cleavage of the side chain by ozonolysis, [26] and subsequent transformation of the resulting aldehyde 17 [23] . A Julia‐like, two‐step alkene synthesis was employed, rather than one step procedures like the Wittig reaction, since this resulted in higher yields [27] .…”

Section: Resultsmentioning

confidence: 99%

“…In the past, several semisyntheses of demethylgorgosterol ( 1 b ) and its stereoisomers, as well as one of gorgosterol ( 1 a ), were achieved by the groups of Djerassi and Ikekawa. The first attempts to methylenate a suitable precursor using either a Simmons‐Smith reaction or a Corey‐Chaykovsky reaction did not yield the desired configuration [23] . All of the following syntheses used an intramolecular 3‐exo‐tet ring‐closure strategy to form the cyclopropane moiety in the desired configuration (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

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Formal Semisynthesis of Demethylgorgosterol Utilizing a Stereoselective Intermolecular Cyclopropanation Reaction

et al. 2021

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In this study, we report a convenient and high yielding formal semisynthesis of demethylgorgosterol, a marine steroid with an intriguing sidechain containing a cyclopropane unit. This was achieved through the synthesis of an advanced ketone intermediate. The synthetic route features a total of ten steps, starting from commercially available stigmasterol, with an overall yield of 27 %. The key step was a stereoselective intermolecular cyclopropanation reaction. This reaction proceeded in 82 % yield, the resulting cyclopropane carboxylic ester shows a trans/cis ratio of 89 : 11, with a diastereomeric ratio for the trans‐diastereomers of >99 : 1. A reduction/oxidation sequence afforded the corresponding aldehyde, which was used in a Grignard reaction. A final oxidation step then yielded the desired ketone. This novel route presents a platform to further investigate the medicinal applications of gorgosterol‐type steroids and to fully understand their role in coral symbiosis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Formal Semisynthesis of Demethylgorgosterol Utilizing a Stereoselective Intermolecular Cyclopropanation Reaction

et al. 2021

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“…The initial attempts to construct side chains of cathasterone 21, cryptolide 22, and brassinolide 23 (Scheme 4) were performed on the model aldehyde 19, 11 which is available in three steps from stigmasterol. The next step was the key to making the carbon skeleton of the side chain.…”

Section: Resultsmentioning

confidence: 99%

The development and use of a general route to brassinolide, its biosynthetic precursors, metabolites and analogues

et al. 2015

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A new method for the construction of steroid side chains through the addition of lithium salts of dithianes to a C-22 aldehyde was developed. An efficient one-pot procedure for the preparation of a suitable C-22 aldehyde from commercial epibrassinolide in three steps in 86% isolated yield was described. Enantioselective hydroxymethylation of isovaleraldehyde and Kulinkovich cyclopropanation of silylated Roche esters were used as key steps for the dithiane syntheses. The method was applied for the preparation of brassinolide, its biosynthetic precursors and metabolites. In addition, a number of brassinosteroids with a double bond in the side chain were prepared as precursors for tritiated derivatives for biosynthetic studies.

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“…Preparation of the title compounds started from aldehyde 21 22 (Scheme 2) and proceeded through addition of vinylmagnesium bromide to give the allylic alcohol 22 as a mixture of (22S)-and (22R)-diastereomers. 23 The next step was to build a C-24-C-26 fragment of the side chain.…”

Section: Synthesis Of Cholestenoic Acids 9 and 10mentioning

confidence: 99%

Formation of the steroidal C-25 chiral center via the asymmetric alkylation methodology

2015

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A novel approach for the preparation of steroids containing a chiral center at C-25 is reported. The key stereochemistry inducing step was asymmetric alkylation of pseudoephenamine amides of steroidal C-26 acids. The reaction proceeded with high diastereoselectivity (dr > 99 : 1). The developed methodology was successfully applied to the synthesis of (25R)- and (25S)-cholestenoic acids as well as (25R)- and (25S)-26-hydroxy brassinolides.

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Stereoselective synthesis of two stereoisomers of demethylgorgosterol

Cited by 38 publications

References 11 publications

Formal Semisynthesis of Demethylgorgosterol Utilizing a Stereoselective Intermolecular Cyclopropanation Reaction

Formal Semisynthesis of Demethylgorgosterol Utilizing a Stereoselective Intermolecular Cyclopropanation Reaction

The development and use of a general route to brassinolide, its biosynthetic precursors, metabolites and analogues

Formation of the steroidal C-25 chiral center via the asymmetric alkylation methodology

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