Recent Progress in Steroid Synthesis Triggered by the Emergence of New Catalytic Methods

Khatri, Hem Raj; Carney, Nolan; Rutkoski, Ryan; Bhattarai, Bijay; Nagorny, Pavel

doi:10.1002/ejoc.201901466

Cited by 21 publications

(17 citation statements)

References 179 publications

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“…Because of their important bioactivity and diverse structures, steroids play an important role in organic synthesis and drug discovery. [1][2][3][4][5][6][7][8] Phomarol (1) (Figure 1), a C25 steroid with an unusual architecture, was isolated by Jung and co-workers 9 in 2016 from a jellyfish-derived fungus. Structurally, phomarol (1) contains a sterically compact [7-6-6-5-6]-fused pentacyclic framework, with a highly functionalized tetrahydropyran E-ring (highlighted in blue).…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Total Synthesis of Phomarol

Fan

Wang

et al. 2021

CCS Chem

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The first and asymmetric total synthesis of phomarol, an uncommon C25 steroid, is described. The synthetically challenging benzocycloheptane motif, found in phomarol and some other naturally occurring molecules, was synthesized efficiently using a very mild acid-promoted type I [5 + 2] cycloaddition, followed by regio-and chemoselective cleavage of the C-O bond and aromatization cascade. This work is the first example of using the hydrogen bonding between the hydroxy group and oxidopyrylium ylide to control the stereoselectivity of cycloadditions. The highly functionalized tetrahydropyran ring of phomarol was produced efficiently based on our suggested biomimetic pathway.

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Section: Introductionmentioning

confidence: 99%

Asymmetric Total Synthesis of Phomarol

Fan

Wang

et al. 2021

CCS Chem

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“…For many decades total synthesis has played a vital role in the development of various fields and disciplines related to molecular medicine and drug discovery. The tremendous advances in total synthesis over past several decades would not have been possible without breakthroughs in synthetic methodology and catalysis, and asymmetric catalysis in particular [1,2]. The role chiral catalysts play for chemical synthesis extends far beyond their original use for controlling the enantioselective formation of product, and many modern applications of chiral catalysts are focused on imposing diastereoselectivity [3] and site-selectivity in complex settings [4].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of C2-Symmetric SPIROL-Based bis-Oxazoline Ligands

2021

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This communication describes the synthesis of new bis-oxazoline chiral ligands (SPIROX) derived from the C2-symmetric spirocyclic scaffold (SPIROL). The readily available (R,R,R)-SPIROL (2) previously developed by our group was subjected to a three-step sequence that provided key diacid intermediate (R,R,R)-7 in 75% yield. This intermediate was subsequently coupled with (R)- and (S)-phenylglycinols to provide diastereomeric products, the cyclization of which led to two diastereomeric SPIROX ligands (R,R,R,R,R)-3a and (R,R,R,S,S)-3b in 85% and 79% yield, respectively. The complexation of (R,R,R,R,R)-3a and (R,R,R,S,S)-3b with CuCl and Cu(OTf)2 resulted in active catalysts that promoted the asymmetric reaction of α-diazopropionate and phenol. The resultant O-H insertion product was formed in 88% yield, and with excellent selectivity (97% ee) when ligand (R,R,R,R,R)-3a was used.

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“…[61][62][63][64][65][66] In general, radical approach [67][68][69][70][71][72] is widely applied in the field of organic synthesis for the rapid construction of complex molecular architectures [73][74][75] and the total synthesis of natural products under safe and mild conditions. [76][77][78][79][80][81] Even in nature many of oxidation processes catalyzed by heme proteins and metalloporphyrins have proceeded through a radical mechanism. [82] These attractive features are the reason why we focus in this review on the promising powerful and highly selective radical cross-coupling reactions which have been applied for the asymmetric synthesis of challenging unusual non-proteinogenic AAs.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, owing to the generally mild reaction conditions and often high functional group tolerance, radical chemistry represents a well‐suited strategy for chemoselective modifications of peptides and proteins . In general, radical approach is widely applied in the field of organic synthesis for the rapid construction of complex molecular architectures and the total synthesis of natural products under safe and mild conditions . Even in nature many of oxidation processes catalyzed by heme proteins and metalloporphyrins have proceeded through a radical mechanism …”

Section: Introductionmentioning

confidence: 99%

Advances in Asymmetric Amino Acid Synthesis Enabled by Radical Chemistry

2020

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Chiral amino acids (AAs), being the main "building" blocks of the living organisms, are also an important class of organic compounds which broadly applied in synthetic chemistry, biochemistry, catalysis and the designing of new drugs. According to the industrial-commodity market, chiral non-proteinogenic AAs containing various functional groups come to the fore. To date, radical cross-coupling reactions are becoming an option as an attractive powerful tool for AA syntheses. Owing to mild reaction conditions and high functional-group tolerance, radical chemistry represents an ideal strategy for the synthesis of challenging complex non-proteinogenic AAs. Moreover, the radical cross-coupling allows introducing AA residue into drug scaffolds and natural compounds. In the present review, we wish to summarize and discuss all the reported to date methods of the asymmetric synthesis of AAs using radical chemistry by presenting a comprehensive account of the literature in this field going back to 1990. We especially emphasize on a radical chemistry approach and, exclusively, on stereoselective synthesis of various α-, β-, γ-AAs and derivatives employing a different type of radical initiators starting from AIBN and organostannes and ending with powerful photoredox catalysis. Furthermore, the mechanism of the reported reactions will be discussed. Radicals Generated from AA Derivatives in Conjugate Additions 6.1. Radicals Generated from α-Substituted Glycine Derivatives in AA Synthesis 6.2. Modification of Chiral AA Side Chain by Radical Chemistry 7.

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Recent Progress in Steroid Synthesis Triggered by the Emergence of New Catalytic Methods

Cited by 21 publications

References 179 publications

Asymmetric Total Synthesis of Phomarol

Asymmetric Total Synthesis of Phomarol

Synthesis and Evaluation of C2-Symmetric SPIROL-Based bis-Oxazoline Ligands

Advances in Asymmetric Amino Acid Synthesis Enabled by Radical Chemistry

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