An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B

Haidle, Andrew M.; Myers, Andrew G.

doi:10.1073/pnas.0402111101

Cited by 84 publications

(58 citation statements)

References 48 publications

(60 reference statements)

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“…A number of laboratories have worked towards total synthesis of the cytochalasin family and developed linear 3 or convergent 4 strategies for their total synthesis. Total synthesis of cytochalasin congeners was accomplished by the laboratories of Stork,3a,4a Thomas,3b,3c,3e,3f Trost, 4d Vedejs (zygosporin E), 4b,4c,4e Myers, 5 Liu and Tang (periconiasins A-E) 6 and Nay (periconiasin G). 7 To the best of our knowledge, total synthesis of cytochalasin with a 12-membered macrocyclic ring has not been reported.…”

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confidence: 99%

Synthesis of C14–C21 acid fragments of cytochalasin Z₈via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling

Han

2018

RSC Adv.

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An efficient synthesis of the C14-C21 acid fragment of cytochalasin Z 8 was accomplished in 10 steps with 14% overall yield. Boron-mediated anti-selective aldol condensation and Pd(OAc) 2 -Aphos-Y-catalysed Balkyl Suzuki-Miyaura cross-coupling were employed to construct the requisite C17 and C18 stereogenic centres and alkene subunit.Cytochalasins are secondary fungal metabolites with a wide range of biological activities that target cytoskeletal processes. 1Cytochalasins Z 7 -Z 9 (1-3, Chart 1) were isolated from the marine-derived fungus Spicaria elegans, and their structures and absolute congurations were established by Zhu et al. Cytochalasin Z 8 (2, Chart 1) is structurally related to cytochalasins Z 7 and Z 9 and features highly substituted hydroisoindol-1-one fused with a 12-membered macrolactone ring at the C-8 and C-9 positions. Cytochalasin Z 8 has been reported to exert cytotoxicity against P388 and A-549 cell lines with IC50 values of 56 and 21 mM, respectively, and therefore has signicant potential in cell biology and medicine. A number of laboratories have worked towards total synthesis of the cytochalasin family and developed linear 3 or convergent 4 strategies for their total synthesis. Total synthesis of cytochalasin congeners was accomplished by the laboratories of Stork, 3a,4a Thomas, 3b,3c,3e,3f Trost, 4d Vedejs (zygosporin E), 4b,4c,4e Myers, 5 Liu and Tang (periconiasins A-E) 6 and Nay (periconiasin G).7 To the best of our knowledge, total synthesis of cytochalasin with a 12-membered macrocyclic ring has not been reported. The intriguing molecular architecture and potent biological activity of cytochalasin Z 8 prompted us to pursue its total synthesis and render it to be readily available for biological investigations.The retrosynthetic strategy is depicted in Scheme 1. Intramolecular ring-closing metathesis (RCM) strategy 8 which is a promising tool for constructing macrolactone is oen used for synthesising macrolides. 9 We envisioned an RCM reaction at C13 and C14 positions and an esterication for assembling a 12-membered macrolactone. Thus, acid fragment 4 was required for the total synthesis of 2. Our strategy was exible and it allowed rapid access to structural analogues. In this study, we report the synthesis of C14-C21 acid fragment 4 via a highly anti-selective aldol condensation 10 of aldehyde 6 with Abiko's chiral norephedrine-derived propionate (1R,2S)-7 (ref. 11) and B-alkyl Suzuki-Miyaura cross-coupling 12 of chiral alkyl iodide 5 with (Z)-1-bromoprop-1-ene.Our rst task was to construct C16-C18 syn-anti stereotriad.13 The aldehyde functionality in 6 was expected to undergo an anti-selective aldol reaction with the (E)-boron enolate generated from Abiko's chiral propionate 7 for installing C17-C18 anti stereochemistry according to our synthetic strategy in Scheme 1. We initially prepared crude aldehyde 6 from commercially available (S)-methyl 3-hydroxy-2-methyl propionate (Roche ester) 14 by tosylation and partial ester reduction 15(Scheme 2). The unstable crude aldeh...

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confidence: 99%

Synthesis of C14–C21 acid fragments of cytochalasin Z₈via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling

Han

2018

RSC Adv.

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“…[50] One of the key steps is a diastereoselective intramolecular Diels-Alder reaction of an optically active precursor 68 which originates from l-phenylalanine in 8 steps with 58% yield (Scheme 20).…”

Section: [4 þ 2] Cycloadditionsmentioning

confidence: 99%

Stereoselective Construction of Quaternary Stereocenters

2005

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“…Cytochalasin exhibited IC 100 values of 3.91, 15.6, and 3.91 μg/ mL, respectively. Cytochalasins are known to induce apoptosis by inhibiting cell division due to their ability to bind with, and inhibit the polymerization of, actin fi laments (Haidle and Myers 2004 ). Cytoglobosins C and D were isolated and identifi ed from endophytic fungus Chaetomium globosum QEN-14.…”

Section: Alkaloidsmentioning

confidence: 99%

Endophytic Fungi: Novel Sources of Anticancer Molecules

Kumar

Rai

Gaur

et al. 2013

Advances in Endophytic Research

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Cancer is an enormous global health burden, touching every region of the world. The term "anticancer" is based on the assessment of the authors of the paper of the cytotoxicity of each compound against specifi c cancer cell lines. Endophytic fungi, fungi that are residing asymptomatically in internal tissues of all higher plants, are of growing interest as promising sources of biologically active agents. Endophytic fungi are one of the most creative groups of secondary metabolite producers that play important biological roles for human life. This chapter mainly focuses on endophytic fungi, which produce anticancer bioactive compounds such as paclitaxel, podophyllotoxin, camptothecin, vinblastine, hypericin, and diosgenin. The uniqueness of the endophytic community of fungi is stressed as a promising source of novel compounds with anticancer activity. Endophytes represent a dependable source of specifi c secondary metabolites and can be manipulated both physicochemically and genetically to increase yields of desired metabolites and to produce novel analogues of active metabolites.

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An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B

Cited by 84 publications

References 48 publications

Synthesis of C14–C21 acid fragments of cytochalasin Z₈via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling

Synthesis of C14–C21 acid fragments of cytochalasin Z₈via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling

Stereoselective Construction of Quaternary Stereocenters

Endophytic Fungi: Novel Sources of Anticancer Molecules

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An enantioselective, modular, and general route to the cytochalasins: Synthesis of L-696,474 and cytochalasin B

Cited by 84 publications

References 48 publications

Synthesis of C14–C21 acid fragments of cytochalasin Z8via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling

Synthesis of C14–C21 acid fragments of cytochalasin Z8via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling

Stereoselective Construction of Quaternary Stereocenters

Endophytic Fungi: Novel Sources of Anticancer Molecules

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Synthesis of C14–C21 acid fragments of cytochalasin Z₈via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling

Synthesis of C14–C21 acid fragments of cytochalasin Z₈via anti-selective aldol condensation and B-alkyl Suzuki–Miyaura cross-coupling