Bicyclic molecule

About: Bicyclic molecule is a research topic. Over the lifetime, 29587 publications have been published within this topic receiving 451252 citations. The topic is also known as: bicyclic molecule.

Synthesis and conformational analysis of a non-amidine factor Xa inhibitor that incorporates 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 binding element.

Abstract: Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.

Synthesis of conduritols and related compounds

Abstract: New and stereospecific syntheses for all conduritol isomers have been developed starting from appropriate 1.3-cyclohexadiene derivatives. Oxygen functionalities were introduced by photooxygenation. Application of the ene-reaction of singlet oxygen to 1.4-cyclohexadiene and its derivatives afforded diene system which can be easily trapped by second mol of singlet oxygen to give 49 and 50. Thiourea reduction of the peroxide linkages followed by oxidation gave the corresponding pent01 derivatives. Furthermore, reaction of unsaturated endoperoxides with 1.2.4.5- temine derivatives 59-63 afforded new bicyclic endoperoxides with unusual structures.

Additions to bicyclic olefins. III. Stereochemistry of the epoxidation of norbornene, 7,7-dimethylnorbornene, and related bicyclic olefins. Steric effects in the 7,7-dimethylnorbornyl system

Abstract: A systematic study of addition reactions of norbornene, 7,7-dimethylnorbornene, and related bicyclic olefins has been undertaken in order to define more precisely the role of steric effects in controlling the stereo- chemistry of the additions and the nature of the intermediates in such addition reactions. The addition of borane to norbornene proceeds almost exclusively exo (99.573, whereas the corresponding addition to 7,7-dimethylnor- bornene proceeds preferentially endu (78%). Similarly, hydroboration of 2methylenenorbornane gives pref- erentially exo (85%), whereas 2-methylene-7,7-dimethylnorbornane gives preferentially (85%) endo product. Similar results were realized with 1-methylnorbornene, 2-methylnorbornene, bornene, and 2,7,7-trimethylnorbor- nene. Consequently, hydroboration of norbornene, 1- and 2-methylnorbornene, and 2-methylenenorbornane goes predominantly exo, evidently reflecting the greater steric availability of the exu position in this bicyclic system. However, the presence of 7,7-dimethyl substituents causes the addition to proceed preferentially from the endu direction. Consequently, in hydroboration the 7,7-dimethyl substituents alter the normal direction of addition to olefins of the norbornane structure, irrespective of whether the double bond is endocyclic, directly under the 7,7- substituents, or exocyclic, located to the side of the substituents. major argument for the u-bridged norbornyl cation A is the almost exclusive exo substitution realized in the solvolysis of 7,7-dimethylnorbornyl derivatives. 334