Synthetic studies of thiazoline and thiazolidine-containing natural products — 2. Total synthesis of the antimycoplasma antibiotic micacocidin

Ino, Akira; Hasegawa, Yasushi; Murabayashi, Akira

doi:10.1016/s0040-4020(99)00583-9

Cited by 32 publications

(21 citation statements)

References 10 publications

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“…25 In similar fashion, reaction with either 2,4-dinitrobenzenesulfonyl chloride or with 3-nitro-2-pyridinesulfenyl chloride also failed. 26,27 In all cases, either recovery of starting material or extensive decomposition of the diketopiperazine 17 on prolonged reaction times was observed. We therefore elected to carry out a two-stage deprotection of the para-methoxybenzyl group.…”

Section: Methodsmentioning

confidence: 94%

An Expedient Entry into the α-Mercaptodiketopiperazine Nucleus

Hilton¹,

Motherwell²,

Selwood³

2004

Synlett

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A novel approach to the a-mercaptodiketopiperazine nucleus is reported, which involved a three-component reaction of a number of amines with ethyl glyoxalate and para-methoxybenzylmercaptan. The subsequent products were readily elaborated to the monothiodiketopiperazine core structure.The epidithiodiketopiperazines 1 as exemplified most notably by gliotoxin (2, Figure 1), are a structurally diverse class of secondary fungal metabolites, which display a very wide spectrum of biological activity. 1 Thus gliotoxin (2) exhibits potent antiviral/antifungal activity and has also been shown to cleave DNA in vitro. 2 The biological activity of this natural product family stems from the unique geometrical constraints which are imposed by precise location of the disulfide bridge across the cyclic dipeptide in such a way as to facilitate cleavage of the sulfur-sulfur bond either by thiol exchange or reduction. 3 In connection with a research programme designed to probe the nature and reactivity of thiyl radicals in such systems a range of simple a-mercaptodiketopiperazine derivatives were required. Herein, we now report our initial results on a convenient route to the simplest derivatives of this class. Figure 1From a synthetic standpoint, the complexity and structural diversity inherent within these molecules has stimulated interest in the development of generally applicable methods for construction of the core unit (1). 4-16 Almost invariably however, these have centred around the incorporation of both sulfur atoms into a preformed diketopiperazine. The introduction of a protected dithioacetal building block by Kishi, 6,7 which relies on a double bromination-thioacetate displacement sequence originally introduced by Trown has been used by several groups and is illustrative. [6][7][8]16,17 Since such an approach is not tolerant of more sensitive functionality, we therefore elected to adopt an alternative strategy, which involved the introduction of one of the two sulfur atoms at an early stage. Thus, as outlined in Scheme 1, our primary objectives were to develop an efficient method for the synthesis of aalkylthio glycine derivatives 3, which were then suitable for simple elaboration to differentially, protected monothiodiketopiperazines (4). Formation of target epidithiodiketopiperazines could then be achieved using methodology previously developed by Ottenheijm. 12,13 Herein we now report our preliminary studies in this area. Scheme 1In the first instance, we were attracted to a report by Badet which involved an elegant three-component coupling of amides or carbamates with glyoxalate and isopropyl thiol. 18 In terms of our own requirements, we elected to examine the reactions of tert-butyl carbamate and methyl carbamate with para-methoxybenzylmercaptan and ethyl glyoxalate (Scheme 2). Unfortunately however, all attempts to achieve subsequent deprotection of the carbamates 9 and 10 for further elaboration towards monoalkylthiodiketopiperazines were unsuccessful.In light of these results, albeit that the products 12 (Schem...

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Section: Methodsmentioning

confidence: 94%

An Expedient Entry into the α-Mercaptodiketopiperazine Nucleus

Hilton¹,

Motherwell²,

Selwood³

2004

Synlett

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“…Thus, thiazolines are important building blocks in pharmaceutical agents and biologically active natural products with antibiotic properties, like micacocidin [17,18]. Besides, the other five-membered heterocycle present in this work, thiazolidine ring, is a constituent part of penicillins framework [19].…”

Section: Introductionmentioning

confidence: 93%

Synthesis, structural characterization and influence on the phagocytic activity of human neutrophils of thiazoline and thiazine derivative ligands and their zinc(II) complexes

Barros-García

Bernalte‐García

Lozano-Vila

et al. 2006

Journal of Inorganic Biochemistry

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“…2-Alkylthiazolidines exhibit radioprotective, antimutagenic, antibacterial, and antiviral activity [3,8]. Compounds of the thiazolidine series are important as models for studying biochemical transformations of their complex analogs involved in natural processes [9].Hydrolytic stability of the above listed heterocyclic compounds is an important factor determining their application as therapeutic agents which undergo cleavage of the heteroring in vivo [10,11]. It is known that L-cysteine responsible for intracellular level of glutathione could be introduced at a required dose as appropriate prodrugs, 2-alkylthiazolidines [10,11].…”

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confidence: 99%

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Regioselectivity of the hydrolysis of 2-(1-alkoxyvinyl)-substituted imidazolidines, 1,3-thiazolidines, and 1,3-oxazolidines

et al. 2011

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2-(1-Alkoxyvinyl)-1,3-thiazolidines reacted with H 2 O or D 2 O in the presence of 105 mol % of p-toluenesulfonic acid or trifluoroacetic acid (20°C, 1 h) to give 2-acetyl-1,3-thiazolidine in quantitative yield. 2-(1-Alkoxyvinyl)-3,5-diphenylimidazolidines underwent hydrolysis in the presence of 20 mol % of an acid (20°C, 24 h) at the vinyloxy group with high regioselectivity yielding 2-acetylimidazolidines. Hydrolysis of 2-(1-alkoxyvinyl)-3-phenyl-1,3-oxazolidines in the presence of 10 mol % of p-toluenesulfonic acid (20°C, 5 days) takes two pathways, one of which involves the endocyclic C-O bond with ring opening and the other involves the vinyloxy group to produce 2-acetyl-3-phenyl-1,3-oxazolidine. Unlike phenyl-substituted 1,3-thiazolidines and imidazolidines, hydrolysis of their 3-methyl-and 3,5-dimethyl-substituted analogs in acid medium occurs mainly via ring opening. The observed hydrolysis pathways were interpreted in terms of B3PW91/6-311G(d,p) quantum-chemical calculations.Interest in the chemistry of 2-alkyl-[1] and 2-acyl-1,3-oxazolidines [2], 2-alkyl-[3] and 2-acetyl-1,3-thiazolidines [4], 2-alkylimidazolidines [5], and 2-acetylimidazolidines [6] is related to the presence of the corresponding fragments as structural units of many medical agents and natural compounds, as well as to their use as starting compounds for the synthesis of pharmaceuticals and fragrant substances. In particular, some 2-acyloxazolidines are convenient precursors in the synthesis of alkaloids [7]. 2-Alkylthiazolidines exhibit radioprotective, antimutagenic, antibacterial, and antiviral activity [3,8]. Compounds of the thiazolidine series are important as models for studying biochemical transformations of their complex analogs involved in natural processes [9].Hydrolytic stability of the above listed heterocyclic compounds is an important factor determining their application as therapeutic agents which undergo cleavage of the heteroring in vivo [10,11]. It is known that L-cysteine responsible for intracellular level of glutathione could be introduced at a required dose as appropriate prodrugs, 2-alkylthiazolidines [10,11]. The nitrogen-containing heteroring in vivo undergoes nonenzymatic hydrolysis to release amino acid and the corresponding aldehyde. The mechanism of acid hydrolysis of some 1,3-thiazolidines was studied in vitro [12]. The results of kinetic studies on hydrolytic ring opening in 2-aryl-N-methyl(phenyl)oxazolidines showed that the rate of hydrolysis and optimal pH value often strongly depend on the nature and/or stereochemistry of substituents in the oxazolidine ring [13].We previously found that 2-alkoxypropenals readily react with 2-aminoalkanols [14], 2-aminoethanethiol [15], and ethane-1,2-diamines [16] to give the corresponding 2-(1-alkoxyvinyl)-1,3-oxazolidines, -1,3-thiazolidines, and -imidazolidines as mixtures with their open-chain tautomers. The fraction of the cyclic structure decreases as the solvent polarity rises [15,16],

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Synthetic studies of thiazoline and thiazolidine-containing natural products — 2. Total synthesis of the antimycoplasma antibiotic micacocidin

Cited by 32 publications

References 10 publications

An Expedient Entry into the α-Mercaptodiketopiperazine Nucleus

An Expedient Entry into the α-Mercaptodiketopiperazine Nucleus

Synthesis, structural characterization and influence on the phagocytic activity of human neutrophils of thiazoline and thiazine derivative ligands and their zinc(II) complexes

Regioselectivity of the hydrolysis of 2-(1-alkoxyvinyl)-substituted imidazolidines, 1,3-thiazolidines, and 1,3-oxazolidines

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