Novel Enantioselective Synthesis of α-Methylthreonines and α,β-Dimethylcysteines

Shao, Hui; Rueter, Jaimie K.; Goodman, Murray

doi:10.1021/jo971983u

Cited by 56 publications

(39 citation statements)

References 16 publications

(14 reference statements)

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“…[41] This protected amino acid was then coupled to doubly protected L-aaminoadipic acid using iso-butylchloroformate methodology. [42] Then caesium carbonate-mediated coupling of the dipeptide and (2S)-a-bromoisovaleric acid tert-butyl ester was accomplished following the procedure of Lerchen and Kunz, [43] prior to trifluoroacetic acid deprotection [44] to give the substrate analogue AmCOV 15.…”

Section: Methodsmentioning

confidence: 99%

Unexpected Oxidation of a Depsipeptide Substrate Analogue in Crystalline Isopenicillin N Synthase

et al. 2006

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Isopenicillin N synthase (IPNS) is a non-heme iron(ii)-dependent oxidase that is central to penicillin biosynthesis. Herein, we report mechanistic studies of the IPNS reaction in the crystalline state, using the substrate analogue delta-(L-alpha-aminoadipoyl)-(3R)-methyl-L-cysteine D-alpha-hydroxyisovaleryl ester (AmCOV) to probe the early stages of the catalytic cycle. The X-ray crystal structure of the anaerobic IPNS:Fe(II):AmCOV complex was solved to 1.40 A resolution, and it reveals several subtle differences in the active site relative to the complex of the enzyme with its natural substrate. The crystalline IPNS:Fe(II):AmCOV complex was then exposed to oxygen gas at high pressure; this brought about reaction to give what appears to be a hydroxymethyl/ene-thiol product. A mechanism for this reaction is proposed. These results offer further insight into the delicate interplay of steric and electronic effects in the IPNS active site and the mechanistic intricacies of this remarkable enzyme.

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Section: Methodsmentioning

confidence: 99%

Unexpected Oxidation of a Depsipeptide Substrate Analogue in Crystalline Isopenicillin N Synthase

et al. 2006

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“…[12,13] We decided to use molecular modelling to investigate the approximate stereochemical course of the AD. Only a few reports on the AD of olefins have dealt with an ''abnormal'' sense of asymmetric induction.…”

Section: Principlesmentioning

confidence: 99%

Molecular Dynamics-Based Models Explain the Unexpected Diastereoselectivity of the Sharpless Asymmetric Dihydroxylation of Allyl D-Xylosides

et al. 2000

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The catalytic asymmetric dihydroxylation of several allyl 2‐O‐benzyl‐α‐D‐xylosides with AD‐mix β and PYR(DHQD)2 shows almost no diastereofacial selectivity if the 3‐ and 4‐OH groups are unprotected or acetylated. Acetal, benzyl ethers and benzoyl esters enhance the diastereoselectivity, in the opposite sense to that predicted by the “AD mnemonic”, which is completely lost using AD‐mix α. In an attempt to understand this behaviour, computational studies of the asymmetric dihydroxylation (AD) of olefins using Sharpless' and Corey's catalysts have been carried out using molecular dynamics. A three‐step algorithm was developed taking advantage of the enzyme‐like behaviour of catalyst‐olefin systems and applied using an ESFF force field. To validate our approach, the first sampling step procedure was then refined and performed using a modified CVFF force field. This led to a U‐shaped model in good agreement with that proposed by Corey for the AD of allyl 4‐methoxybenzoates, which brings to the fore a role for the methoxy group. This model also accounts for the observed enantioselectivity of styrene dihydroxylation. When applied to the AD of allyl xylosides using AD‐mix β, our model accounts well for the observed diastereoselectivity. Both synthetic and modelling results confirmed that aromatic groups on the olefin could be involved in π‐π stacking interactions with the aromatic rings of the catalyst and should be important, if not a prerequisite, to achieve high enantio‐ and diastereoselectivity.

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“…To the best of our knowledge, the trisubstituted C=C bond of angelic acid esters 3 (Figure 1), and derivatives thereof, is the only SAD site at which, according to the literature, configurational control was incongruent, at least in one instance contradictory, and in part in conflict with the Sharpless mnemonic (Scheme , see below) 11–19. This investigation unravels the steric course of the SAD of esters and amides of methacrylic acid,20 tiglic acid,21 and angelic acid22 unambiguously (see below); enantiomerically pure (in most cases) or enriched (occasionally) 1,2‐diols obtained from such substrates were used in the construction of complex natural products,20k,21b,21c represented drug candidates,20h,20j served as building blocks for peptides [20a,20c,20e–20g,21a,22b] or became the progenitor of other diverse products.…”

Section: Introductionmentioning

confidence: 89%

Asymmetric Dihydroxylation of Esters and Amides of Methacrylic, Tiglic, and Angelic Acid: No Exception to the Sharpless Mnemonic!

Weber

Brückner

2015

Eur J Org Chem

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Novel Enantioselective Synthesis of α-Methylthreonines and α,β-Dimethylcysteines

Cited by 56 publications

References 16 publications

Unexpected Oxidation of a Depsipeptide Substrate Analogue in Crystalline Isopenicillin N Synthase

Unexpected Oxidation of a Depsipeptide Substrate Analogue in Crystalline Isopenicillin N Synthase

Molecular Dynamics-Based Models Explain the Unexpected Diastereoselectivity of the Sharpless Asymmetric Dihydroxylation of Allyl D-Xylosides

Asymmetric Dihydroxylation of Esters and Amides of Methacrylic, Tiglic, and Angelic Acid: No Exception to the Sharpless Mnemonic!

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