Tricyclic, lactams

S—Cg is perpendicular to the amide plane of the / -lactam and therefore weakened. The S—bond, on the other hand, is not affected by electronic interactions with the benzamide plane. It was now thought, that a bridging of the thiazolidine moiety would bring the —S bond into a more orthogonal position with respect to the amide plane of the new lactam and make this bond more fragile. The tricyclic thiazolidine was synthesized as described above and fulfilled the predictions (J.E. Baldwin, 1978). 

A simple entry towards bi-and tricyclic N-oxy-/i-lactams by high pressure promoted tandem [4 + 2]/[3 + 2] cycloadditions of end ethers and /i-nitrostyrene [65]... 

Dipolar cycloaddition of azides with olefins provides a convenient access to triazolines, cyclic imines, and aziridines and hence is a valuable technique in heterocyclic synthesis. For instance, tricyclic -lactams 273 - 276 have been synthesized using the intramolecular azide-olefin cycloaddition (lAOC) methodology (Scheme 30) [71]. 

The benzocarbacephems 22 (Fig. 11.12), with (X = Cl or F) or without (X = H) a halogen leaving group, were synthesized by a copper-mediated intramolecular aromatic substitution as the main step.73 74 These tricyclic (3-lactams are also competitive inhibitors of (3-lactamases and not substrates. 

A similar approach was used by the Alcaide group [183] in the synthesis of tricyclic (3-lactams 6/1-391 from 6/1-390 (Scheme 6/1.99). In this domino process the primarily obtained it-allyl-Pd-complex reacts with the N-nucleophile of the urethane moiety to form a C-N-bond and a vinyl halide. The final step is then an intramolecular Heck-type reaction of the vinyl halide with the alkyne moiety and re-... 

The synthetic potential of the tandem [4+2]/[3+2] cycloaddition process is greatly enhanced by the employment of vinyl ether dienophiles. For example, the use of vinyl butyl ether as a dienophile leads to a tricyclic nitroso acetal, which gives a tricyclic lactam, as shown in Eq. 8.113. 

Lactam sulfonium salts bearing a dihydrothiopyran skeleton with a sulfonio bridgehead have been synthesized. Tricyclic benzothiazinium salts 87 were prepared by [4+2+]-polar cycloaddition of a thionium intermediate 99, generated from the corresponding a-chloro sulfide 98, in the presence of silver perchlorate in moderate to good yields (see Equation (28) and Table 17) <1997J(P1)309>. Cycloaddition with isoprene 41b gave adducts 87b and 87c as a... 

The stereoselective synthesis of classical trinems (fused tricyclic systems having the azetidin-2-one nucleus fused through the N-C4 bond) <98MI347> and the chemistry of non-classical polycyclic P-lactams have been reviewed <00T5743>. 

Grigg has utilized the Heck reaction in several ways, from the simple cyclization of N-(2-iodobenzoyl)pyrrole (139) to afford tricyclic lactam (140) [100] to the complex cascade... 

Trost used a Sonogashira coupling, followed by reduction of the nitro group, to prepare 350, which in turn was converted to tricyclic lactam 351 by Pd-catalyzed cyclization (yield unreported) [309],... 

The aromatic rings of allene carboxanilides 149 also acted as the diene to furnish the tricyclic lactams 150 in refluxing xylene or benzene [125]. 

In addition to the two asymmetric syntheses above described, two racemic syntheses of tetraponerines based on the 5=6-5 tricyclic skeleton have been published. Thus, Plehiers et al. [199] have reported a short and practical synthesis of ( )-decahydro-5Tf-dipyrrolo[l,2-a r,2/-c]pyrimidine-5-carbonitrile (238), a pivotal intermediate in the synthesis of racemic tetraponerines-1, -2, -5 and -6, in three steps and 24% overall yield from simple and inexpensive starting materials. The key reaction of the synthesis was a one-pot stereoselective multistep process, whereupon two molecules of A pyrroline react with diethylmalonate to afford the tricyclic lactam ester 239, possessing the 5-6-5 skeleton (Scheme 10). Hydrolysis of the carboethoxy group of 239 followed by decarboxylation yielded lactam 240, that was converted into a-aminonitrile 238 identical in all respects with the pivotal intermediate described by Yue et al. [200] in their tetraponerine synthesis. 

Another study focused on aryl-substituted P-lactams, using the same set of teicoplanin-based CSPs and variable-temperature conditions [99]. Tricyclic P-lactams were investigated by the same group of authors, together with some bicyclic P-amino acids, on five different commercially available glycopeptides CSPs, namely ristocetin A, TE, TAG, vancomycin, and VAG, and on a new dimethylphenyl carbamate-derivatized 5-cyclodextrin-based CSP. The chromatographic results, achieved with different methods, were compared in systematic examinations [170]. 

Cyclizing ca-chloro Reissert compound 136 gives rise to tricyclic lactam 137 (72JHC541). In a study of the cobalt-mediated reaction of pyridones with alkynes, in the case of the N-hexynyl compound, C-H activation with... 

Hence, lithium salt 343a is trapped by aldehydes, and subsequent intramolecular attack of the intermediate alkoxide on the lactam moiety leads to pyridinophanes 405a and b. Ethanolysis of lactam 288 under acidic or basic conditions, even at —78°C, affords ester 406, whereas the reactions of lactams 288 and 290 with 4-methyl-l,2,4-triazoledione (MXAD) give mixtures of cycloadducts 407a and b or the respective isoquinolines. Tricyclic 290 when irradiated suffers loss of carbon monoxide to form butadiene 408. 

A series of bi- and tricyclic pyridoazepine-type lactams was studied as conformationally restrained peptide mimetics acting as ACE inhibitors or dual inhibitors, that is both ACE and neutral endopeptidase (NEP) inhibitors, especially by the groups of Flynn and Robl. ACE and NEP are zinc metalloproteases acting as vasopeptidases. The respective inhibitors are used in the treatment of hypertension, congestive heart failure, and other cardiovascular diseases. 

Chiral bicyclic lactams have been successfully utilized by Meyers as chiral dipolarophiles in highly diastereoselective azomethine ylide cycloadditions (73). Treatment of the ylide precursor 218 with the unsaturated, non-racemic dipolar-ophile 219 in the presence of a catalytic amount of TFA led to the formation of tricyclic adducts 220 and 221 in excellent yields (85-100%). The diastereofacial preference for the reaction was dependent on the nature of R with a methyl group... 

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