Zaragozic Acid A/Squalestatin S1: Synthetic and Retrosynthetic Studies

Nicolaou, K. C.; Yue, Eddy W.; Naniwa, Y.; Riccardis, Francesco De; Nadin, Alan; Leresche, James E.; Greca, Susan La; Yang, Zhen

doi:10.1002/anie.199421841

Cited by 51 publications

(12 citation statements)

References 40 publications

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“…This new 4-step synthesis of alcohol 7 , in 22% overall yield and in 97% ee, has distinct advantages over previously reported asymmetric syntheses of this pheromone in terms of stereochemical purity, number of steps, and total yield . Furthermore, the chiral γ-methyl-α,β-enoate structural unit is present in many natural products, including steroids, macrolides, and squalestatins . The scalability of this short protocol was confirmed when 2.8 g of γ-methyl ester 3a was synthesized in 60% overall yield and 95% ee starting with commercial 3-phenylpropanal .…”

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confidence: 99%

α-Chloro-β,γ-ethylenic Esters: Enantiocontrolled Synthesis and Substitutions

et al. 2010

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Chiral nonracemic γ-seleno-α,β-ethylenic esters, when treated with sulfuryl chloride and ethyl vinyl ether in hexanes, produced α-chloro-β,γ-ethylenic esters in 65-75% yields, with ee values of 95-97%, and with 1,3-syn transfer of chirality. Reaction of these allylic chloride electrophiles with methylcuprate and with sodium azide nucleophiles afforded exclusively γ-substituted-α,β-ethylenic esters with faithful anti-transfer of chirality on multigram scale.

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confidence: 99%

α-Chloro-β,γ-ethylenic Esters: Enantiocontrolled Synthesis and Substitutions

et al. 2010

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“…Compound 9 is the enantiomer of Nicolaousi ntermediate,w hich was initially synthesized in 12 steps with 81 % ee. [16] To further illustrate the usefulness of this methodology, we continued to explore its potential in the synthesis of gbutyrolactones (Scheme 3), which are important structural units of aw ide range of pharmacologically active molecules. [17] Ozonolysis of the desymmetrized product of 10 followed by hydroxy-directed Wittig reaction [18] afforded the unsaturated ester (4S,5S)-12 as asingle isomer with excellent d.r.…”

Section: Methodsmentioning

confidence: 99%

Site‐ and Enantioselective Iridium‐Catalyzed Desymmetric Mono‐Hydrogenation of 1,4‐Dienes

Schulze

et al. 2021

Angewandte Chemie

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The control of site selectivity in asymmetric mono‐hydrogenation of dienes or polyenes remains largely underdeveloped. Herein, we present a highly efficient desymmetrization of 1,4‐dienes via iridium‐catalyzed site‐ and enantioselective hydrogenation. This methodology demonstrates the first iridium‐catalyzed hydrogenative desymmetriation of meso dienes and provides a concise approach to the installation of two vicinal stereogenic centers adjacent to an alkene. High isolated yields (up to 96 %) and excellent diastereo‐ and enantioselectivities (up to 99:1 d.r. and 99 % ee) were obtained for a series of divinyl carbinol and divinyl carbinamide substrates. DFT calculations reveal that an interaction between the hydroxy oxygen and the reacting hydride is responsible for the stereoselectivity of the desymmetrization of the divinyl carbinol. Based on the calculated energy profiles, a model that simulates product distribution over time was applied to show an intuitive kinetics of this process. The usefulness of the methodology was demonstrated by the synthesis of the key intermediates of natural products zaragozic acid A and (+)‐invictolide.

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“…To introduce the (8R,9R)-diol functionality, lactone 41 was subjected to dihydroxylation conditions using ADmix-b, as established in the synthesis of fostriecin 1; however, these conditions turned out to be unsatisfactory in terms of reproducibility. After exploring various conditions, we eventually found that reaction of 41 with Super-AD-mix, 35 using the ligand for Sharpless asymmetric dihydroxylation [(DHQD) 2 PHAL] as a chiral ligand, resulted in highly diastereoselective dihydroxylation preferentially at the D 8 -double bond to give diol 42 together with its 6,7-dihydroxy isomer in a ratio of 87:13; however, very high regioselectivity was not observed in this case, unlike the dihydroxylation of 14 discussed above.…”

Section: Scheme 8 Preparation Of Aldehyde 33mentioning

confidence: 99%

Total Synthesis of (+)-Fostriecin and (+)-Phoslactomycin B

Shibahara¹,

Fujino²,

Tashiro³

et al. 2009

Synthesis

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+)-Fostriecin and (+)-phoslactomycin B, which are potent and selective inhibitors of protein phosphatase, were synthesized by a highly enantio-and stereoselective approach that enabled us to prepare all possible isomers at both the C11 secondary alcohol position and the D 12 -double bond.The soil bacteria species Streptomyces produce a series of structurally novel antifungal and antitumor antibiotics that include fostriecin, 1 PD113,271, 1 the phoslactomycins A-F and I, 2 the phosphazomycins C 1 and C 2 , 3 and the leustroducsins A-C and H. 2e,4 These compounds are highly potent and selective inhibitors of protein serine/threonine phosphatase 2A, which may account for their antitumor activity. 5,6 Because of their intriguing molecular architectures and their potential as a lead compounds for anticancer drugs, as well as their importance as biological tools, this class of compounds has attracted much attention in the chemical and biological communities. 7 As a result, there have been a number of formal and total syntheses of fostriecin, 5a,8,9 PD113,271, 10 leustroducsin B, 11,12 and phoslactomycin A and B, 13 including ours. Here, we describe details of our total syntheses of (+)-fostriecin (1) 9f and (+)-phoslactomycin B (2); 13c the methods used also enabled us to prepare various analogues of these compounds.The close structural similarity between (+)-fostriecin (1) and (+)-phoslactomycin B (2) allowed us to devise a common synthetic plan, which is illustrated in Scheme 1. We envisaged ynone 7 as a precursor to make our approach flexible. We expected that the advanced intermediate 3, as well as its stereoisomers 4, 5, and 6, would each be available from 7 by a combination of stereoselective formation of the (E)-or (Z)-iodoenone 14 and C9-OH directed anti-or syn-selective reduction. 15 To access 7, we envisaged an approach from alcohol 8 involving ring-closing metathesis 16 and Sharpless asymmetric dihydroxylation, 17 both of which were thought to be challenging in terms of selectivity because of the possibility of reaction occurring at several sites. In addition, the key issues to be addressed for the synthesis of 2 were stereoselective construction of the C4 asymmetric center and the installation of the C8 asymmetric quaternary center along with its aminoethyl substituent. Scheme 1 Retrosynthetic analysis of fostriecin and phoslactomycin BThe synthesis of fostriecin (1) began with the stereoselective preparation of trienol 12 (Scheme 2). 2,3-Dihydrofuran was first converted into the (3E)-4-(tributylstannyl)pent-3-en-1-ol with complete E-selectivity by means of Aldisson's procedure. 18 (3E)-4-(Tributylstannyl)pent-3-en-1-ol was subjected to p-methoxybenzylation to give the ether 9, which was iodinated to give alkenyl iodide 10. Heck reaction 19 of the iodide 10 with acrolein, gave the aldehyde 11. Brown's asymmetric allylation 20 of 11 gave alcohol 12 in good yield. The optical purity of 12 was not determined at this stage because of its instability both under the conditions for HPLC analysis on a chiral column...

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Zaragozic Acid A/Squalestatin S1: Synthetic and Retrosynthetic Studies

Cited by 51 publications

References 40 publications

α-Chloro-β,γ-ethylenic Esters: Enantiocontrolled Synthesis and Substitutions

α-Chloro-β,γ-ethylenic Esters: Enantiocontrolled Synthesis and Substitutions

Site‐ and Enantioselective Iridium‐Catalyzed Desymmetric Mono‐Hydrogenation of 1,4‐Dienes

Total Synthesis of (+)-Fostriecin and (+)-Phoslactomycin B

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