Sulfur-Directed Regioselective Radical Cyclization Leading to .beta.-Lactams: Formal Synthesis of (.+-.)-PS-5 and (+)-Thienamycin

Ishibashi, Hiroyuki; Kameoka, C.; Iriyama, Hiroko; Kodama, Kazuya; Sato, T.; Ikeda, Masazumi

doi:10.1021/jo00110a035

Cited by 70 publications

(25 citation statements)

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“…7 To screen for catalytic activity, we performed the reactions under the following defined conditions: 90 mM of donor, 130 mM of acceptor and 9 mol% antibody in PBS (pH¼7.4) at room temperature. Control experiments revealed that, in the absence of antibody, no reactions take place under these conditions (entries 1,3,5,7,9). For the antibody-mediated reactions, we found that all the reactions were taking place in the presence of ab84G3 with the exception of the reaction of acetone with 2-phenylthiobutyraldehyde 8 (entry 10).…”

Section: Resultsmentioning

confidence: 77%

A biocatalytic route to enantioenriched, sulfanyl aldol products

2004

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Section: Resultsmentioning

confidence: 77%

A biocatalytic route to enantioenriched, sulfanyl aldol products

2004

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“…These intermediates would rapidly equilibrate, and hydrogen atom abstraction from the thiol by the less hindered radical C , according to the precedent of Montevecchi and co-workers,9 should afford cis -β-thioenamide D as the kinetic product. In contrast, known methods of β-thioenamide construction based on imine acylation10 or Pummerer rearrangement11 chemistry deliver predominantly the trans isomers. We also recognized that the presence of excess thiol in the reaction mixture would permit isomerization of D to the thermodynamically more stable trans isomer via a radical addition–β-thiyl radical elimination pathway 12.…”

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confidence: 99%

Stereoselective Additions of Thiyl Radicals to Terminal Ynamides

et al. 2010

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Two complementary sets of conditions for radical additions of thiols to terminal ynamides are described. The use of 1 equiv of thiol affords the cis-β-thioenamide adducts in rapid fashion (10 min) and good dr, whereas employing excess thiol and longer reaction times favors the trans products.Ynamides are a class of compounds that have gained prominence in recent years. 1 They are electron-rich alkynes, 2 although their nucleophilicity can be tuned by varying the nature of the N-acyl group. Malacria has demonstrated the utility of ynamides as radical acceptors. 3,4 We reasoned that they should react readily with thiyl radicals, which are electrophilic in nature. 5 A recent report by Yorimitsu and Oshima detailing radical additions of arenethiols to internal tosylynamides 6 lent support to this hypothesis.The addition of a thiyl radical to an ynamide produces a β-thioenamide. This moiety is present in unusual cyclic peptides such as thioviridamide 7 (Figure 1) and the lantibiotics. 8 Inspired by the striking architecture of these natural products, we investigated additions of thiyl radicals to terminal ynamides. Herein, we report the initial results of our study, which demonstrate that both cis and trans β-thioenamides can be obtained selectively by simply varying the reaction conditions.The proposed reaction is shown in Figure 2. Regioselective addition of a thiyl radical to the terminal carbon of ynamide A would provide vinyl radicals B and/or C. These intermediates would rapidly equilibrate, and hydrogen atom abstraction from the thiol by the less hindered radical C, according to the precedent of Montevecchi and co-workers, 9 should afford cis-β-thioenamide D as the kinetic product. In contrast, known methods of β-thioenamide construction based on imine acylation 10 or Pummerer rearrangement 11 chemistry deliver predominantly the trans isomers. We also recognized that the presence of excess thiol in the reaction mixture would permit isomerization of D to the thermodynamically more stable trans isomer via a radical addition-β-thiyl radical elimination pathway. 12 Accordingly, we pursued a stereoselective synthesis of both cis-and trans-β-thioenamides by seeking two complementary sets of reaction conditions. We began by studying the additions of commercially available thiols to simple ynamides. Our results are collected in Table 1. Addition of excess n-butyl thiol (4 equiv) to acyclic amide- derived ynamide 1 13 in refluxing t-BuOH with AIBN as initiator 14 afforded β-thioenamide E-3a as the major product of a separable mixture (72%, 15:1 E:Z) after 3 h. In contrast, employing 1 equiv of thiol and 0.5 equiv of AIBN led to Z-3a in good yield (76%, 1:11 E:Z) after only 10 min. Similar trends were observed with thiophenol, although greater quantities of the E isomer were obtained under both sets of conditions. When the radical addition of tert-butyl thiol to 1 was performed under the Z-selective conditions, no reaction was observed. Subjection of this bulky thiol to the typically E-selective conditions a...

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“…The substitution reaction between aryl thiol 1 and bromoacetaldehyde acetal 16 was performed in the presence of one equivalent of sodium ethoxide. Acidic hydrolysis of the dimethyl acetal 17 yielded aldehyde 18, [41] which was then converted into oxime 19. Sulfone 20 was prepared by oxidation with oxone, and then the oxime moiety was reduced to N-hydroxyethylamine 21 using sodium cyanoborohydride at room temperature.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Evaluation of New Antagonists of Bacterial Quorum Sensing in Vibrio harveyi

Peng

Cheng

et al. 2009

ChemMedChem

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Bacterial quorum sensing has received much attention in recent years because of its relevance to pathological events such as biofilm formation. Based on the structures of two lead inhibitors (IC50: 35-55 microM) against autoinducer-2-mediated quorum sensing identified through virtual screening, we synthesized 39 analogues and examined their inhibitory activities. Twelve of these new analogues showed equal or better inhibitory activities than the lead inhibitors. The best compound showed an IC50 value of approximately 6 microM in a whole-cell assay using Vibrio harveyi as the model organism. The structure-activity relationship is discussed herein.

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Sulfur-Directed Regioselective Radical Cyclization Leading to .beta.-Lactams: Formal Synthesis of (.+-.)-PS-5 and (+)-Thienamycin

Cited by 70 publications

References 0 publications

A biocatalytic route to enantioenriched, sulfanyl aldol products

A biocatalytic route to enantioenriched, sulfanyl aldol products

Stereoselective Additions of Thiyl Radicals to Terminal Ynamides

Synthesis and Evaluation of New Antagonists of Bacterial Quorum Sensing in Vibrio harveyi

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