Thiazoline system synthesis

In this synthesis the formation of the thiazoline system 31 32 is carried out at 0 C in ether. Thus a good yield and a high degree of stereoselectivity (> 4 1) is achieved. 

Hansa Yellows, 1, 334 5, 299 Hantzsch synthesis, 2, 87-88 1,4-dihydropyridine, 2, 482 thiazoles, 6, 294-299 A -thiazolines, 6, 314 Hantzsch-Widman names parent names, 1, 35 stem suffixes, 1, 12 Hantzsch-Widman system nomenclature, 1, 11-12 Hardeners in photography... 

The first phase of the total synthesis of thiostrepton 303, a highly complex thiopeptide antibiotic, has been described. Retrosynthetic analysis of thiostrepton revealed units 304-308 as potential key building blocks. Concise and stereoselective constructions of all these intermediates have been achieved. The synthesis of the dehydropiperidine core 308 was based on a biosynthetically inspired aza-Diels-Alder dimerization of an appropriate azadiene system, an approach that was initially plagued with several problems which were, however, resolved satisfactorily by systematic investigations. The quinaldic acid fragment 305 and the thiazoline-thiazole segment 306 were synthesized by a series of reactions that included asymmetric and other stereoselective processes (Scheme 113) <2005JA11159>. 

A number of phosphonate and phosphinate derivatives where the phosphorus atom is directly bonded to non-aromatic cyclic systems have been reported. The synthesis and reactions of a number of compounds with the general structure 103 have been reported. Enantiomerically pure cyclopropanephosphonic acids which are constrained analogues of the GABA antagonist phaclophen, have been prepared by stereocontrolled Michael addition of a-anions derived from chiral chloromethylphosphonamides 104 to a,P-unsaturated esters followed by in situ cyclisation. Other asymmetric syntheses include those of (/ )- and (S)-piper-idin-2-ylphosphonic acid (105) via the addition to trialkyl phosphites to iminium salt equivalents and 4-thiazolidinylphosphonate 106 by catalytic asymmetric hydrophosphonylation of 3-thiazoline. In the latter case both titanium and lanthanoid (which give much better e.e. values) chiral catalysts are used. 

In this connection must also be cited the work done on the thiazoline-thione ring system in the elucidation of the structure of penicillin and the synthesis of this and related compounds. 

The first preliminary studies towards the synthesis of penam derivatives by the Ugi reaction were carried out roughly 30 years ago. 3-Thiazoline derivatives (153) were allowed to react with isocyanides in the two-phase system water/petroleum ether to yield up to 95% of the penam derivatives (154). 

The synthesis of 2-amino-6//-l,3,4-thiadiazines (276) by condensation of a-haloketones (274) with thiosemicarbazides, as first reported by Bose <25JIC51,25JIC95) continues to be used as a reliable route to this system. The reaction, however, can be complex and the products are dependent on the nature of the substituents in each of the reactants, the polarity of the solvent used, and the reaction temperature <91CHE666> common by-products are 2-hydrazinothiazoles (275) and 3-amino-thiazolines (see Section 6.17.5.2). An excellent review of the confusing and sometimes erroneous pioneering work on these reactions is available . 

An application arising from the extensive research on penicillin is outlined in Scheme 5A Here, the synthesis of the bicycMc ring system found in penicillin was accomplished by generating ketene 5.33 in the presence of thiazoline 5.34, which is participating as an imine. Ketenes are readily prepared by this process... 

Mohammadpoor-Baltork and colleagues also investigated the scope and generality of this catalytic system by the synthesis of 2-imidazolines (20) (Table 1.9, entries 1-6) and 2-thiazolines (21) (Table 1.9, entries 7-12). The reactions were carried out starting from different types of arylnitriles and ethylenediamine or 2-aminoethanethiol, respectively, under the same reaction conditions used in the synthesis of 2-oxazolines, obtaining the corresponding derivatives in good to excellent yields. 

Synthesis.—In following the practice adopted in Elderfield s treatises on heterocyclic compounds the syntheses of benzothiazoles and benzo-thiazolines are again classified according to the nature of the fragments from which the ring system is built up. The letters designating the type of synthesis correspond to previous usage as closely as practicable. 

Acheson and his group have continued their work on the reactions of DMAD, and have shown that the products (307) and (308) obtained from benzimidazolin-2-thione (306) are dependent upon the solvent used. The benzo-thiazoline ring system has also been included in the search for potential antibiotics, with the synthesis of (309) from 4-acetoxyazetidinone. ... 

A novel, biogenetic-type synthesis of the penicillin and cephalosporin ring-systems has been described. The key step in this approach is a stereo-controlled cyclization of the acyclic tripeptide (171) to the cu-)3-lactam (172), an intermediate which may be transformed into both penicillin and cephalosporins (Scheme 6). Alternatively, an oxidative cyclization of thiazoline (173) ulti-... 

The search for novel p-lactam antibiotics has been severely restricted by the relative inaccessibility of these ring systems by stereospecific total syntheses. Because of the availability of both the penicillin and, more recently, cephalosporin nuclei from fermentation processes, partial synthesis of new ring systems from these starting materials has been extensively investigated. The penicillin-cephalosporin interconversions continue to be studied while new degradative procedures have permitted the synthesis of useful snythons by complete removal of the thiazoline ring of penicillin. 

Imidaz6[2,l-b]thiazoles (132) are further obtainable in good yield from 2-aminothiazoles (131) by the action of phenylacyl bromide, " or from 2-imino-3-(2-propynyl)-A -thiazolines (133) by alkahne cyclization. Thiocyanation of (132) and (134) yields the corresponding 5-thiocyanato-derivatives. The synthesis by established routes of further examples of this ring-system has been recorded. ... 

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