Guanidine tricycle

Boyer and co-workers" also reported the synthesis of the guanidine tricycle (122), prepared as the tetrahydrochloride salt from the condensation of two equivalents of guanidine with 1,4-diformyl-2,3,5,6-tetrahydroxypiperazine in concentrated hydrochloric acid. Treatment of the tricycle (122) with absolute nitric acid yields thebis-nitrimine (123), whereas the same reaction with nitric acid-acetic anhydride yields HHTDD (117). 

Cyclocondensation of 3-cyano-2-methylthio-4//-pyrido[l, 2-u]pyrimidin-4-ones and ethyl mercaptoacetate in boiling EtOH in the presence of NaOEt afforded 4//-pyrido[l,2-u]thieno[2,3-r/ pyrimidin-4-ones 210 (00HC571). 2-Methylthio-4-oxo-4//-pyrido[l,2-u]pyrimidine-3-carboxylates 211 and mercaptoacetates afforded tricyclic derivatives 212 (93MIP1). Cyclocondensation of 2-methylthio-4-oxo-4//-pyrido[l, 2-u]pyrimidin-3-car-bonitriles 213 with H2NNH2 H2O and with guanidine HCl afforded tricyclic derivatives 214 and 215, respectively (96FES781). 

Treatment of 8-azidomethylperhydropyrido[l,2-c]pyrimidin-l-one 157 with methyl triflate and catalytic hydrogenation of the azide group led to the formation of tricyclic guanidine derivative 158 (01JA8851). Hydroxy group of 149 was protected with methoxymethyl chloride, and the p-methoxybenzyl protecting group (PMB) was eliminated by treatment with DDQ. 

In an approach toward substituted guanidines, Louwrier and co-workers observed an unusual reaction whereby reaction of the /3-ketoester 310 with bis-BOC-thiourea 311 in the presence of HgCl2 and triethylamine gave the tricyclic product 312 in excellent yield <1996T2629>. The mechanism that the authors suggest to account for this product, via intermediates 314-316, is outlined in Scheme 23. 

Saxitoxin is a small tricyclic structure isolated from oceanic red tides it has attracted much interest for its peculiar structure and toxicity as a paralytic agent. The core structure that is related to a l-iminooctahydropyrrolo[l,2-f]-pyrimidine nucleus was prepared by rearrangement after oxidation of a double bond contained in a medium-size guanidine ring. This key intermediate in the synthesis was prepared from azide 376 with a judicious use of Mbs... 

The novel structure of cylindrospermopsin, with a guanidine embedded in a tricyclic system, six chiral centers, and polar sulfate, uracil and guanidine functional groups, makes its synthesis challenging. Its potent toxicity makes the synthesis of cylindrospermopsin an important problem that has been the subject of intense interest.1,7 8... 

The key step in the synthesis was bromination of ketone 59, followed by hydrogenation to liberate the free guanidine, which underwent an intramolecular Sn2 reaction to form the tetrahydropyrimidine ring B. Further hydrogenation reduced the ketone to yield 42% of 63 containing the fully functionalized tricyclic system and protected hydroxymethyl-uracil side chain of cylindrospermopsin. Hydrolysis of the pyrimidine of 63 in concentrated hydrochloric acid at reflux and selective monosulfation completed the synthesis of cylindrospermopsin. 

Finally, two polycyclic systems were built. First, the cyclic guanidine embedded into the 2-aminobenzimidazole nucleus 9.20a-f was used to buM the tricyclic library L9 (7680 members. Fig. 9.13) then a complex spiro-piolyheterocycle library LIO... 

Cylindrospermopsin (CYN) is an alkaloid containing a tricyclic guanidine combined with hydroxymethyl uracyl (Figure 27.1C) with a molecular weight of 415 daltons. Intraperitoneal injection of cells containing CYN in mice is followed by diarrhea, anorexia, irregular respiration, and... 

The reaction between [l,3,4]thiadiazolo[2,3-cn[l,2,4]triazolo[l,5a][l,3,5]triazinium halides 116 and primary or secondary amines afforded highly substituted guanidines 118 and fused tricyclic bis([l,2,4]triazolo)[l,5-a r5 -< [l,3,5]triazinium halides 119. The reaction occurs through novel intermediate triazinium-imidothioate zwitterions 117 one of which was characterized by X-ray analysis <05T673>. 

Guanidine metabolites of Ptilocaulis spiculifer and related compounds (marine alkaloids with tricyclic guanidine fragment) isolation and synthesis 00CSR57. 

The Wittig-type reactions of iminophosphoranes with isocyanates and related compounds have also been extensively used in heterocyclic synthesis. Examples include the preparations of the mesoionic [l,3,4]thiadiazolo[2,3-c][l,2,4]triazines (210) from (209), 0 bicyclic guanidines, e.g. (212), from (211), naphthypyridines (215), (216), and (217) from (213) and (214), 2 pyrido[l,2-f]pyrimido-[4,5-d)pyrimidines (218), 7H-pyrido-[4,3-c]- (219) and 10H-pyrido[3,4-b]- (220) carbazoles, tricyclic fused 2,4-diimino-l,3-diazetidines (222) from the bisiminophosphorane (221), benzotriazepines (225) from (223) and (224), 6 and mesoionic thiazolo-[2,3-b]-1,3,4-thiadiazoles (227) and N,N-bisheteroarylamines from the iminophosphorane (226), derived from 3-amino-4-phenylthiazole-2(3H)-thione. The carbodiimides (229), prepared from the iminophosphorane (228), can be converted into quinolines or a-carboline derivatives depending on the nature of the isocyanate used in the reaction with (228) and the reactions of iminophosphoranes (230) and (231) with aryl and styryl isocyanates provide one-pot syntheses of quinoline, a-carboline, and quinindoline derivatives. 9... 

Tricyclic sulfoxides carrying an iminoester function can isomerize to alternative imines in the presence of catalytic amidine or guanidine under mild conditions through [ 13]-proton transfer [91]. Modest asymmetric induction (up to 45% ee) was observed in the use of the Corey s guanidine (20) (Table 4.14). 

Cylindrospermopsin is an alkaloid consisting of a tricyclic guanidine coupled with hydrox3unethyluracil (Figure 31.2). It is a zwitterionic, highly water-soluble molecule (Ohtani et al., 1992). There are two known structural variants deoxycylindrospermopsin (Norris et al., 1999), which is relatively less toxic, and 7-epicyl-indrospermopsin (Banker et al., 2001), which is relatively... 

Marine alkaloids (-f)-batzelladine A and ( )-batzel-ladine D. Nine novel tricyclic guanidine marine alkaloids were isolated as metabolites of the Crambe genus. Members of the batzelladine alkaloid class exhibit potential antiviral activity in the inhibition of HIV gp 120-Human CD4 binding, as well as potential immunosuppressive... 

Thioureas have also been synthesized by aminolysis of other thiocarbonic acid derivatives. Carbon disulphide reacted with guanidines to yield RNHC(S)NH2 along with 1,3,5-thiadiazines (14). The tricyclic compound (15) was formed by... 

Sorek, H., Rudi, A., Gueta, S., Reyes, F., Martin, M.J., Aknin, M., Gaydou, E., Vacelet, J., and Kashman, Y. (2006a) Netamines A-G seven new tricyclic guanidine alkaloids fiom the marine sponge Biemna laboutei. Tetrahedron, 62, 8838-8843. 

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