Methylthio compounds, synthesis

Synthesis of the methylthio compounds followed a route previously used for the cyclohexyl analogs (18) and is depicted in Scheme 8 the starting material is readily available (19) by a Dieckmann condensation of the acetal (CH3)3CCH(SCH2CO2C2H5)2 ... 

Mention has already been made of attempts to obtain 2-hydroxy- and 3-hydroxypenams (compounds 301 and 303), from which penems might have been generated by loss of the elements of water. The reductive elimination performed on the 2,3-diphenylthiopenam 316 by Kametani [182], and the oxidative elimination accomplished by Hanessian on the 2-methylthio compound 298 [29], are successful examples of penem synthesis achieved from isolated penam intermediates. Other examples of this strategy involve Pummerer-type rearrangements. The preparation of penem 306 by treatment of penam sulfoxide... 

Deoxy-5 -(cyclopropylmethylthlo)adenosine (70) has been prepared from 5 -chloroadenosine,l23 and there has been a further report on the synthesis of 5 -(fluoromethylthio)adenosine (71), formed with the 5 -fluoro-5 -methylthio compound discussed last year (see Vol.22, p. 212) from reaction of the 5 -methylsulphinyl derivative with DAST. Thioether (71) is a potent inhibitor of methylthioadenoslne phosphorylase.i24 An oxidation-reduction... 

The synthesis of 5-methoxy-l,3,4-thiadiazole-2(3H)-thione (114) by the successive treatment of Omethyl thiocarbazate (112) with carbon disulphide and alkali proceeds normally. However, addition of the reagents in the inverse order results in the isomeric 5-methylthio-compound (113) by a transmethylation process, for which a possible mechanism was proposed. ... 

P212121 Z = 4 D = 2.01 R = 0.04 for 1,611 intensities. The compound is a minor product in the synthesis of methyl tyveloside. The pyranose conformation is a distorted 4, with Q = 66 pm 6= 162° (p=H8a. The (methylthio)carbonyl side-chain is extended. The C-S bond-lengths are 174.8, 179.1 pm. The C-I bond-length is 215.2 pm. The absolute configuration was confirmed by using the anomalous-scattering factors of the iodine atoms. 

For the synthetic studies on the bicyclic 6-6 systems 1-3, with one ring junction nitrogen and five extra heteroatoms, refer to CHEC-II(1996) <1996CHEC-II(8)743>. In the studies of the newly available compounds, a one-pot procedure for the synthesis of [l,2,4]triazino-[4,3- ][l,2,4,5]tetrazine 4 derivatives is discussed below. Refluxing of hydrazonoyl halides 10 in chloroform (or ethanol) in the presence of triethylamine for 6h with either 4-amino-2,3-dihydro-6-substituted-3-thioxo-[l,2,4]triazin-5(4//)-ones 8 or 4-amino-3-methylthio-6-substituted-[l,2,4]-triazin-5(4//)-ones 9 yielded compounds 4 (Equation 1) <2000JPR342>. 

Cyclisation of an NH amide toward a cyclic thionium ion was described for the synthesis of a tetrahydropyrrolo-[l,2-tf]pyrimidine-2,6(l//,7//)-dione 351. Compound 349 was transformed to 351 in two steps. The first one is the formation of a transient alkylthio-substituted lactam 350 from amidothioacetal 349 in the presence of dimethyl-(methylthio)sulfonium tetrafluoborate (DMTSF) followed by intramolecular cyclization <2000JOC235>. 

The final step in the synthesis of the thiadiazole nucleoside (178) is achieved by prolonged treatment of (179) with methanolic sodium methoxide (Equation (25)) <82AHC(32)285). Reaction of the A"-1,2,4-thiadiazoline (180) with dry HCl in methanol leads to the 2-carbamoyl compound (181). When (180) is treated with a mixture of free amines and amine hydrochlorides in the ratio of 2 1 in refluxing ethanol, 2-amidino-3-imino-5-methylthio derivatives (182) are formed in good yield (Scheme 42) <84CHEC-i(6)463>. 

These heterocycles (240) are the first representatives of meso-ionic compounds to be S3mthesized in which the raocyclic subsfituent f. Table I) is a stabilized carbanionoid group [-C(CN)C02Me or -CfChOi]-Their synthesis d involves the reaction between (i) JV-aminoamidines (23 ) and bis(methylthio)acrylonitriles (241), (ii) iV-thioacylhydrazines (232), and 3-alkylamino-3-methylthioacrylonitriles (242), and (iii) 1,2,4-triazolium iodides (234, R = Me, X = I) and malononitrile. 

The chlorosulfonium compounds can also be used for the synthesis of oxindoles, the stable tautomeric form of 2-hydroxyindoles. The a -methylthio ketone is replaced by ethyl methylthioacetate and the products of the Sommelet-Hauser rearrangement are cyclized to 3-methylthiooxindoles. The methylthiooxindoles are reductively desulfurized with Raney nickel (equation 102) (74JA5508). 

Umbraculumin C (90), characterized by the presence of a trans-3-(methylthio)-acrylic acyl residue, is a diacylglycerol obtained from the skin of the opisthobranch mollusc Umbraculum mediterraneum [96]. Taylor and co-workers determined the absolute configuration of 90 by total synthesis [97] while Sodano et al. reached the same conclusion by derivatisation of the natural compound [98]. Compound 90 displayed ichthyotoxic activity against the mosquito fish at 0.1 pg/ml and should represent the deterrent of this organism against predators [96]. 

About 6 years later, Broom and Srinivasan [76] described the synthesis of the 5-deaza-5-oxo analogues ((85a) and (85b), respectively) of AP and MTX Scheme 3.17). Beginning with ethyl 4-amino-2-methylthio-5-oxopyrido-[2,3-d]pyrimidine-6-carboxylate (82), readily available in four steps from 2-methylthio-4,6-diaminopyrimidine (81) [77], they prepared the diaminoalcohol (83) in three steps. Conversion of (83) to the bromomethyl compound (84) was followed by reaction with (31) or (35) and saponification to generate the target compounds (85a) and (85b). At about the same time, it was reported that (80a)... 

Methylthio)thiophene, with trinuclear Os clusters, 6, 744 Methyltin hydride, synthesis, 3, 844 Methyltitanation, alkynes, 10, 256 Methylzirconocene ester enolates, preparation, 4, 923 Methylzirconocene pyrazolyl compounds, preparation,... 

More recently, Wolfrom and Foster found that the d and l enantio-morphs of methyl 3,4-0-isopropylidene-2-0-[(methylthio)thiocarbonyl]-/3-arabinop3Tanoside rearrange, on pyrolysis, to the appropriate 2-methyl-thio)carbonyl] esters. The reductive desulfurization of methyl 3,4-0-isopropylidene-2- S - [(methylthio)carbonylj - 2 - thio -/3 - d - arabinopyranoside (LXVIII) with Raney nickel, to afford a low yield of methyl 2-deoxy-3,4-0-isopropylidene-/3-D-erj/intramolecular rearrangement to LXVIII, and the relationship of the transformation to the Chugaev reaction was discussed. 

---