Kinetics of 1,3-dipolar cycloaddition of a series of meta- and para-substituted diphenyldiazomethanes (DDMs) with fullerenes C60 and C70 as dipolarophiles have been investigated in toluene at 30 degrees C. Fullerene C60 was ca. 1.5 times more reactive than C70. The rate constants (k) for the primary [3 + 2] additions increased with the increase of the electron-releasing ability of the meta and para substituent. The log k/k0 values were well correlated by the Yukawa-Tsuno (Y-T) equations with the smaller negative rho values (-1.6 and -1.7 for C60 and C70) and the reduced resonance reaction constants r (0.22 and 0.17) compared to similar reactions of common acceptors, TCNE, DDQ, and chloranil (CA). The plots of log k (acceptor) versus log k (C60) as reference gave good regression equations and the slopes became larger in the order of TCNE > DDQ > CA > C70 > or = C60. The rates were also found to decrease with the increase of solvent polarity due to the ground-state solvation of fullerenes. However, the relative reactivity of these acceptors toward the unsubstituted DDM increased in the order of DDQ > C60 > or = C70 > TCNE > CA. The unexpected higher reactivity of fullerenes was interpreted in terms of the inherent steric strain by the pyramidalization of the sp2 C-atoms as well as the shorter [6,6] bonds with larger pi-electron densities.

(±)-Phycocyanobilin and its derivatives bearing a photoreactive group at D-ring were first synthesized by the development of a new and convenient method for the preparation of A-ring, transesterification for propanoic acid side-chains of the pyrrole derivative common to B- and C-rings, and deprotection of allyl ester side-chains with a palladium catalyst to avoid migration of exocyclic olefin of A-ring.

We recently reported the synthesis and gastrointestinal prokinetic activity of novel benzamide derivatives with amphoteric side chains.1) Among them, 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetic acid (1a) exhibited the most excellent gastro-and colon-prokinetic activities by intravenous administration to conscious dogs without significant dopamine D 2 receptor antagonist activity. However, 1a showed only weak gastrointestinal prokinetic activity after oral administration due to its low lipophilicity. After the evaluation of several ester prodrugs of 1a, the butyl ester (1b) was consequently selected as a promising gastrointestinal prokinetic agent without significant side effects.As described previously, 1) compound 1b was prepared by esterification of 1a with butyl bromide in a large amount of N,N-dimethylformamide (DMF). The key intermediate 6 was obtained in four steps and an overall yield of 48% from commercially available 4-amino-1-benzylpiperidine (2). A compound 1a was prepared in four steps and an overall yield of 40% from commercially available 4-amino-5-chloro-2-methoxybenzoic acid (7) as shown in Chart 2.Although the previous route was quite adequate for the synthesis with a wide variety of 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidinealkanecarboxylic acids or the assorted ester prodrugs of 1a, the overall yield (14%) of 1b from 2 was not sufficient and a number of steps (9 steps) were required. We have therefore developed a new and facile synthetic route for a high overall yield with only short steps. In this paper, we describe a new and efficient route for the synthesis of 1b.In a new synthetic route, the key intermediate, butyl 4-amino-1-piperidineacetate (16), was prepared as shown in Chart 3. The amino group of 2 was protected with di-tertbutyl dicarbonate (Boc 2 O) in acetonitrile (CH 3 CN) to give compound 112) in 90% yield. Debenzylation of 11 with Pearlman's catalyst 3) and cyclohexene in ethyl alcohol (EtOH) afforded a secondary amine (12) 2) in 92% yield. Alkylation of 12 with butyl chloroacetate (14), 4) which was derived from chloroacetyl chloride (13) and butyl alcohol (nBuOH) in 92% yield, was accomplished using triethylamine (Et 3 N) as a base in DMF to give compound 15 in 93% yield. Since the usage of potassium carbonate (K 2 CO 3 ) as a base in this step produced a great deal of the byproduct, butyl 4-tertbutoxycarbonylamino-1-piperidinecarboxylate, we changed the base from K 2 CO 3 to Et 3 N. Next, the deprotection with hydrogen chloride-isopropyl alcohol solution of 15 followed by the removal of acid using Et 3 N gave a primary amine (16) quantitatively. Compound 7 was converted into the activated ester with ethyl chlorocarbonate (ClCO 2 Et) in anhydrous tetrahydrofuran (THF) and then amidated with 16 to give the desired ester (1b) in good (84%) yield.In conclusion, we have established an efficient route for the synthesis of 1b, a novel promising gastro-and colon-prokinetic agent. The new route shortened the total steps of the synthesis of 1b and cons...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.