Reference

Stereoselective synthesis of 3'-substituted-L-2-(carboxycyclopropyl)glycine derivatives as glutamic acid-receptor blockers

Stereoselective synthesis of 3'-substituted-L-2-(carboxycyclopropyl)glycine derivatives as glutamic acid-receptor blockers. Oofuna, Yasushi; Shimamoto, Keiko; Shinozaki, Atsuhiko; Ishida, Michiko (Suntory, Ltd., Japan). Jpn. Kokai Tokkyo Koho JP 03261748 A2 21 Nov 1991 Heisei, 19 pp. (Japan). CODEN: JKXXAF. CLASS: ICM: C07C229-28. ICS: B01J031-02; C07C227-04; C07C227-22; C07F007-18. ICA: C07B061-00. APPLICATION: JP 90-58750 9 Mar 1990. DOCUMENT TYPE: Patent CA Section: 34 (Amino Acids, Peptides, and Proteins) Section cross-reference(s): 1 The title compd. (I; R = CO2H; R1 = C1-4 alkyl, C7-10 aralkyl, R2 = H) and stereoisomers (II-IV) are prepd. from intermediates, e.Several reagents with their cas registry numbers 139684-29-0 and 2605-67-6 are used here.g. V and VI. Thus, an oxazolidine deriv. (VII; BO = Me3CO2C, TBS = Me3CSiMe2) (prepn. given) was N-deprotected with CF3SO3SiMe3 in 2,6-lutidine/CH2Cl2, diazotized with NaNO2 in aq. citric acid, and then treated with Pd(OAc) in PhMe at 90° for 30 min to give 10% V (R1 = TBS) (VIII) and 33% VI(R1 = TBS). VIII was desilylated with Bu4NF in THF and methylated with MeI in the presence of NaH and Bu4NI in DMF to give 63% V (R1 = Me) which was successively treated with 60% aq. AcOH, Ba(OH)2 in MeOH at 80° for 14 h, and (Me3CO2C)2O in dioxane to give 79% I (R = CH2OH, R1 = Me, R2 = BOC). This was subjected to Jones' oxidn. in Me2CO, deprotection with CF3CO2H in CH2Cl2, and column chromatog. using Dowex 50WX4 to give 28% I (R = CO2H, R1 = Me, R2 = H) (IX). IX, II (R1 = Me) (X), and III (R1 = Me) in vitro showed min. inhibitory concn. of 1 ′ 10-5, 2 ′ 10-5, and 1 ′ 10-3 M, resp., for depolarization activity on motoneuron of newborn rat spinal cord, while IV (R1 = Me) was inactive. IX and X interacted with non-NMPA (N-methyl-D-aspartic acid) receptors, whereas X interacted with NMDA receptors. IX is a glutaminergic agonist which strongly activates kainic acid or quisqualic acid receptors. I-III are useful for treatment of epilepsy and Parkinson's disease. .

The chemistry of indoles

The chemistry of indoles. Part XXI. A facile synthesis of 4-substituted 3-formylindoles. Somei, Masanori; Hasegawa, Toshifumi; Kaneko, Chikara (Fac. Pharm. Sci., Kanazawa Univ., Kanazawa 920, Japan). Heterocycles, 20(10), 1983-5 (English) 1983. CODEN: HTCYAM. 88089-28-5 and 2605-67-6 are also in the experiment. ISSN: 0385-5414. DOCUMENT TYPE: Journal CA Section: 27 (Heterocyclic Compounds (One Hetero Atom)) The 4-indolylthallium trifluoroacetate compd. I was converted to 4-alkenylindoles II (R = MeO, Me) using Pd acetate as a catalyst. I was treated with Me acrylate and Pd acetate in DMF at 120° to give II (R = MeO). 3-Indolecarboxaldehyde was treated with Tl trifluoroacetate in CF3CO2H and Me acrylate and Pd acetate were introduced to yield II (R = MeO). .