Design and synthesis of a novel class of constrained tricyclic pyrrolizidinone carboxylic acids as carbapenem mimics

A series of tricyclic pyrrolizidinone carboxylic acids harboring an angular methano group were synthesized as mimics of carbapenems and carbapenams. A key reaction involved a novel intramolecular cyclopropanation mediated by a trimethylstannylmethyl group and an adjacent iminium ion. Enolate chemistry on a tricyclic lactam ring unit allowed the introduction of various substituents. Further elaboration afforded tricyclic pyrrolidinone carboxylic acids, which were found to be inactive as inhibitors against a panel of bacterial strains. However, the antibacterial activity of ceftazidine was enhanced in the presence of the tricyclic analogues.     

Short and efficient synthesis of a vinyl-substituted tricyclic erythromycin derivative

Tricyclic erythromycin A derivatives are known potent antibacterial agents, but the potential of substituted tricyclic erythromycin A derivatives remains largely unexplored. To study this lead, the tricyclic ring system was synthesized by an efficient three-step synthesis starting from the allylic alcohol utilizing a novel azidoisocyanate. These tricyclic analogues can be used as scaffolds to probe secondary ribosomal binding sites. [structure: see text]     

Unified Asymmetric Total Syntheses of (−)-Alotaketals A–D and (−)-Phorbaketal A

The novel tricyclic spiroketal alotane-type sesterterpenoids showed strikingly different biological activities and potency with subtle structural alterations. Asymmetric total syntheses of the tricyclic sesterterpenoids (−)-alotaketals A–D and (−)-phorbaketal A were accomplished [29–31 steps from (−)-malic acid] in a collective way for the first time. The key features of the strategy included 1) a new cascade cyclization of vinyl epoxy δ-keto-alcohols to forge the common tricyclic spiroketal intermediate, 2) a late-stage allylic C−H oxidation, and 3) olefin cross-metathesis to install the different side chains.     

Synthesis of the 6-6-6 tricyclic skeleton of the anti-influenza A diterpene wickerol A

A five-step synthesis of the 6-6-6 tricyclic skeleton of the diterpene wickerol A is described. The synthesis features a diastereoselective d-proline-mediated Robinson annulation and N-heterocyclic carbene-catalyzed Stetter reaction as key transformations to give the tricyclic carbon skeleton of this promising anti-influenza A natural product.     

Unified Asymmetric Total Syntheses of (−)‐Alotaketals A–D and (−)‐Phorbaketal A

The novel tricyclic spiroketal alotane‐type sesterterpenoids showed strikingly different biological activities and potency with subtle structural alterations. Asymmetric total syntheses of the tricyclic sesterterpenoids (−)‐alotaketals A–D and (−)‐phorbaketal A were accomplished [29–31 steps from (−)‐malic acid] in a collective way for the first time. The key features of the strategy included 1) a new cascade cyclization of vinyl epoxy δ‐keto‐alcohols to forge the common tricyclic spiroketal intermediate, 2) a late‐stage allylic C−H oxidation, and 3) olefin cross‐metathesis to install the different side chains.     

A modular reaction pairing approach to the diversity-oriented synthesis of fused- and bridged-polycyclic sultams

A reaction pairing strategy centered on utilization of a reaction triad (sulfonylation, S(N)Ar addition and Mitsunobu alkylation) generating skeletally diverse, tricyclic and bicyclic benzofused sultams is reported. Pairing sulfonylation and S(N)Ar reactions yields bridged, tricyclic and bicyclic benzofused sultams. Application of the Mitsunobu reaction in a sulfonylation-Mitsunobu-S(N)Ar pairing allows access to benzthiazocine-1,1-dioxides, while a simple change in the order of pairing to sulfonylation-S(N)Ar-Mitsunobu affords structurally different, bridged tricyclic benzofused sultams.     

Synthesis of the [5-7-6] tricyclic core of guanacastepene A via an intramolecular Mukaiyama aldol reaction

[reaction: see text] A synthesis of the tricyclic [5-7-6] skeleton of guanacastepene A is described. The six-membered ring of guanacastepene A was constructed by a Diels-Alder reaction. After several functional group transformations, it was coupled to beta-iodocyclopentenone. Lithium dimethylcuprate conjugate addition followed by an intramolecular Mukaiyama aldol reaction furnished the desired [5-7-6] tricyclic ring system.     

Synthesis of tricyclic heterocycles via a tandem aryl alkylation/heck coupling sequence

A norbornene-mediated palladium-catalyzed sequence is described in which two alkyl-aryl bonds and one alkenyl-aryl bond are formed in one pot with use of microwave irradiation. A variety of symmetrical and unsymmetrical oxygen-, nitrogen-, silicon-, and sulfur-containing tricyclic heterocycles were synthesized from a Heck acceptor and an aryl iodide containing two tethered alkyl halides. This approach was further applied to the synthesis of a tricyclic mescaline analogue.     

A conformationally constrained fused tricyclic nisin AB-ring system mimic toward an improved pyrophosphate binder of lipid II

The bacteria-specific membrane component lipid II is essential for bacterial cell wall synthesis. A tricyclic nisin mimic was designed and synthesized in which both thioether moieties were mimicked by an alkane-bridge, as well as the introduction of a third conformational constraint consisting of a macrocyclic lactam-bridge between the N-terminus and the B-ring. The newly designed tricyclic AB-ring mimic was found to bind lipid II since it was able to inhibit nisin-induced membrane leakage in a dose-dependent manner. These results imply that the tricyclic AB-ring mimic may form a novel class of lead structures for the development of nisin-based peptide antibiotics.     

A facile synthesis of novel tricyclic 4-pyridones

A new and efficient synthesis of tricyclic 4-pyridone analogs through the intramolecular Heck coupling cyclization was described. This reaction features mild conditions and good functional group tolerance allowing for the preparation of several novel tricyclic 4-pyridone analogs.     

Pentacyclic laddersiloxane

A novel method which effects ring extension of the ladder oligosilsesquioxanes was developed. By applying this method, we synthesized the first functionalized tricyclic laddersiloxanes and pentacyclic laddersiloxane. The reaction of (i-PrSi(OH)O)4 with (i-PrPhClSiO)2 in pyridine gave the tetraphenyl tricyclic laddersiloxane. Following dephenylchlorination with AlCl3/HCl, and hydrolysis enabled us to isolate the tetrahydroxyl tricyclic laddersiloxane in good yield. We repeated the similar reaction from this tetrahydroxyl laddersiloxane, and the first pentacyclic laddersiloxane was obtained. The structures of the tetraphenyl and tetrahydroxyl tricyclic laddersiloxanes, and pentacyclic laddersiloxane were determined by X-ray crystallography.     

Stereo‐ and Regioselective Synthesis of Tricyclic Spirolactones by Diastereoisomeric Differentiation of a Collective Key Precursor

A general, parallel, and collective synthesis of 5/5/5‐ and 5/5/6‐ring fusion topologies of tricyclic spiranoid lactones through the controlled cyclizations of easily accessible, common key precursors is described. The rapid composition of key cycloalkyl methylene precursors yielded an assembly of bicyclic diastereoisomeric iodolactones, which were individually converted into a wide range of tricyclic, angularly fused spiranoid lactones in a regioselective and stereodirected fashion through the diastereoisomeric differentiation of a collective key precursor. The critical stereochemical assignment of the bicyclic starting materials, as well as the tricyclic targets, was confirmed by X‐ray crystal structure determination.     

Regioselective synthesis of the tricyclic core of lateriflorone

An efficient synthetic approach to the tricyclic core 8 of lateriflorone is described. Essential to the synthesis was the implementation of a biomimetic tandem Claisen/Diels-Alder reaction that produced the desired tricyclic scaffold as a single isomer. A rationalization of the excellent regio and stereoselectivity of this transformation is also proposed. [reaction: see text]     

Unique strategy for the assembly of the carbon skeleton of guanacastepene A using an allenic Pauson-Khand-type reaction

[reaction: see text] An approach to the highly functionalized tricyclic core of guanacastepene A has been developed using a rhodium(I)-catalyzed allenic Pauson-Khand reaction. This approach constitutes a conceptually novel strategy for the synthesis of this tricyclic framework, whereby the six-membered ring is formed intially followed by simultaneous formation of the five- and seven-membered rings.     

Total Synthesis of Homodimericin A

We report the concise total synthesis of homodimericin A ( 1 ), a recently identified fungal metabolite bearing an unprecedented molecular architecture. The success of the approach hinges on a series of rationally designed and bioinspired transformations, including a Moore rearrangement to assemble the monomeric hydroquinone precursor, homodimerization through double Michael addition to construct the planar A/B/C tricyclic framework, and a tandem Diels–Alder reaction/carbonyl–ene cyclization to forge the congested D/E/F tricyclic cage motif. Unequivocal evidence for the elucidated structure of homodimericin A was also provided by this study.     

Sensitive method for the routine determination tricyclic antidepressants in plasma using a specific nitrogen detector.

The sensitivity of the alkali flame ionization detector to the tricyclic antidepressant drugs has been studied and limits of detection measured. A backflush system has been used to enable measurement in plasma extracts. A general method for the estimation of tricyclic plasma levels has been developed and exemplified by the measurement of imipramine at therapeutic levels.     

Novel tricyclic diamines 2. Synthesis of 1,7-diazaisoadamantane, 1,5-diazaisoadamantane and 1,6-diazahomobrendane

Three novel tricyclic diamines (1,7-diazaisoadamantane, 1,5-diazaisoadamantane and 1,6-diazahomobrendane) were prepared. A flexible synthetic strategy was employed which used flat, aromatic azaindoles as the starting materials. The requisite azaindoles were prepared by a tandem Sonogashira coupling/intramolecular cyclization reaction. Ring saturation, appropriate functionalization and intramolecular alkylation provided the three novel tricyclic diamines cores.     

Studies of Intramolecular Cyclization of 4-Arylpyridines. II Syntheses of Condensed Tricyclic Pyridines

A convenient method for the synthesis of condensed tricyclic pyridines using intramolecular cyclization of 4-arylpyridines is reported. The tricyclic compounds, 2-azafluorenone (9), 2-azafluorenone (10), 2-azafluorenol (11), lactones 12 and 13, and anhydride 14 have been prepared.     

Facile synthesis of the tricyclic core of sarain A. 3-Oxidopyridinium betaine cycloaddition approach

[formula: see text] A new approach to a suitably functionalized tricyclic core of sarains has been developed by means of Katritzky's cycloaddition using 3-oxidopyridinium betaines. A key step was the regioselective differentiation of the two nearly identical hydroxy groups derived from oxidative cleavage of the double bond in 8 to afford 14. A stereocontrolled construction of the tricyclic core 20 of sarains containing the requisite side chain at C-3' was achieved by an intramolecular conjugate addition.     

PdO-Catalyzed Synthesis of Tricyclic Compounds Using Biginelli-Like Reaction

An efficient method has been successfully developed for the synthesis of oxygen-bridged pyrimidine tricyclic derivatives from salicylaldehyde, ethyl acetoacete, and urea catalyzed by PdO in very good yield. A series of different oxygen-bridged pyrimidine tricyclic derivatives has been synthesized, in which two compounds’ x-ray crystal structure were obtained.