Studies on the Synthesis of the Apoptolidins

Chau, Stephen T.; Sulikowski, Gary A.; Wu, Bin

doi:10.1016/b978-0-12-386540-3.00016-2

Cited by 3 publications

(3 citation statements)

References 82 publications

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“…First, the aglycone 3 exhibits comparatively lower mammalian cytotoxicity than the corresponding disaccharride glycosides 1 and 2, consistent with literature reports where the aglycone apoptolidin F exhibits reduced cytotoxicity compared with all other known disaccharride glycoside apoptolidins. 13 Second, and arguably of greater importance, the antimycobacterial activity of amycolatopsins correlate strongly with hydroxylation of the 6-Me (that is, 1 and 3), a site of hydroxylation not previously observed among apoptolidins or ammocidins. Our observations on the amycolatopsins are encouraging in that they suggest a strategy (selective hydroxylation and glycoside hydrolysis) for enhancing antimycobacterial activity across this class of polyketide macrolide.…”

Section: Resultsmentioning

confidence: 89%

“…Detailed analysis of 2D NMR (MeOH-d 4 ) data (Figure 2) revealed diagnostic correlations for a 20-membered macrocyclic lactone (C-1 to C-19) incorporating two triene moieties (C-2 to C-7, and C-10 to C-15), a pendant polysubstituted tetrahydropyran (C-20 to C-28) and three pyranose sugar residues (C-1′ to C-6′, C1′′ to C-6′′ and C-1′′′ to C-6′′′). Double bond geometries (E Δ, 2,3 Z Δ, 4,5 Z Δ, 6,7 E Δ, 8,9 E Δ 10,11 and E Δ 12,13 ) were assigned by consideration of diagnostic rotating-frame Overhauser effect spectroscopy (ROESY) correlations (Figure 2). The relative configuration of the tetrahydropyran moiety was established by ROESY correlations (Figure 2) that positioned H-23 and H-25 on the opposite face to H-22 and H-20.…”

Section: Resultsmentioning

confidence: 99%

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Amycolatopsins A–C: antimycobacterial glycosylated polyketide macrolides from the Australian soil Amycolatopsis sp. MST-108494

Khalil

Salim

Vuong³

et al. 2017

J Antibiot

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A southern Australian soil isolate, Amycolatopsis sp. MST-108494, was subjected to a panel of fermentation and media optimization trials, supported by analytical chemical profiling, to detect and enhance production of a rare class of secondary metabolites. Chemical fractionation of two complementary fermentations yielded three new polyketides, identified by detailed spectroscopic analysis as the glycosylated macrolactones, amycolatopsins A (1), B (2) and C (3), closely related to the ammocidins and apoptolidins. Amycolatopsins 1 and 3 selectively inhibited growth of Mycobacterium bovis (BCG) and Mycobacterium tuberculosis (H37Rv) when compared with other Gram-positive or Gram-negative bacteria, with 3 exhibiting low levels of cytotoxicity toward mammalian cells. Thus, our data reveal promising structure activity relationship correlations where the antimycobacterial properties of amycolatopsins are enhanced by hydroxylation of the 6-Me (that is, 1 and 3), whereas mammalian cytotoxicity is decreased by hydrolysis of the disaccharide moiety (that is, 3).

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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Amycolatopsins A–C: antimycobacterial glycosylated polyketide macrolides from the Australian soil Amycolatopsis sp. MST-108494

Khalil

Salim

Vuong³

et al. 2017

J Antibiot

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“…The groups of Nicolaou [152,153] and Koert [154,155] have presented the first syntheses of apoptolidin A. The groups of Sulikowsky [156,157] and Crimmins [158] have reported syntheses of the aglycon apoptolidinone A. Fragments of this aglycon has been prepared by other groups [159].…”

Section: Generalization Of the So2-induced Umpolung Short Synthesis O...mentioning

confidence: 99%

Expeditious Asymmetric Synthesis of Polypropionates Relying on Sulfur Dioxide-Induced C–C Bond Forming Reactions

Vogel

Gonzalo

2021

Catalysts

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For a long time, the organic chemistry of sulfur dioxide (SO2) consisted of sulfinates that react with carbon electrophiles to generate sulfones. With alkenes and other unsaturated compounds, SO2 generates polymeric materials such as polysulfones. More recently, H-ene, sila-ene and hetero-Diels–Alder reactions of SO2 have been realized under conditions that avoid polymer formation. Sultines resulting from the hetero-Diels–Alder reactions of conjugated dienes and SO2 are formed more rapidly than the corresponding more stable sulfolenes resulting from the cheletropic additions. In the presence of a protic or Lewis acid catalyst, the sultines derived from 1-alkoxydienes are ionized into zwitterionic intermediates bearing 1-alkoxyallylic cation moieties which react with electro-rich alkenes such as enol silyl ethers and allylsilanes with high stereoselectivity. (C–C-bond formation through Umpolung induced by SO2). This produces silyl sulfinates that react with carbon electrophiles to give sulfones (one-pot four component asymmetric synthesis of sulfones), or with Cl2, generating the corresponding sulfonamides that can be reacted in situ with primary and secondary amines (one-pot four component asymmetric synthesis of sulfonamides). Alternatively, Pd-catalyzed desulfinylation generates enantiomerically pure polypropionate stereotriads in one-pot operations. The chirons so obtained are flanked by an ethyl ketone moiety on one side and by a prop-1-en-1-yl carboxylate group on the other. They are ready for two-directional chain elongations, realizing expeditious synthesis of long-chain polypropionates and polyketides. The stereotriads have also been converted into simpler polypropionates such as the cyclohexanone moiety of baconipyrone A and B, Kishi’s stereoheptad unit of rifamycin S, Nicolaou’s C1–C11-fragment and Koert’s C16–CI fragment of apoptolidin A. This has also permitted the first total synthesis of (-)-dolabriferol.

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