Stereospecific synthetic routes are described for the formation of the three contiguous chiral centers in the four diastereomeric 2-aminc-5-phenoxycyclopentanols la-4a. All four stereoisomers (la-4a) were prepared, starting from 3-chlorocyclopentene (6). Among the key steps in the syntheses was the development of a mild method for the formation of the aromatic ether linkage in cis-2-phenoxy-6-oxabicyclo[3.l.0]hexane (9) while maintaining the stereochemistry at the three adjacent centers on the cyclopentane ring. The nucleophilic displacement of the aromatic halogen on a-(chloro-or a-(fluorobenzene)chromium tricarbonyl (19a or 19b) with the anion of the cis-epoxy alcohol 10 proceeded to completion and essentially instantaneously at 45 "C. The presence of an adjacent heteroatom in epoxides 8,9,21, and 24 provided high regiospecificity for the opening of these epoxides by oxygen and nitrogen nucleophiles. X-ray crystallographic analysis of cis-P-amino-trans-5-(4-bromophenoxy)cyclopentanol (27) was used in conjunction with proton NMR spectral data to c o d i the structural assignments of the title compounds. The rationale for the synthesis of 1-4 is briefly discussed.

A number of N,N'-dialkylarylamidines were synthesized and evaluated for antidepressant activity. Several of these compounds were synthesized from the corresponding nitriles by a new method. Slight structural modification in the series caused a marked change in biological activity and led to compounds as active as imipramine. The arylacetamidine, N,N'-dimethyl-2-naphthaleneethanimidamide hydrochloride (33) (napactadine) was selected for clinical study. Forty-eight additional analogues of 33, including a number of N-alkylamidines, were prepared.

Carbon‐14 labeled vigabatrin was synthesized in 5 steps from 5‐hydroxymethyl‐2‐pyrrolidone tosylate and NaCN‐[14C]. A key step involved reduction of the resulting nitrile in the presence of excess dimethylamine to give the dimethylamino‐ethyl 2‐pyrrolidone derivative in one step. This afforded an overall radiochemical yield of 22% and radiochemical purity greater than 98%.

Ausgehend von dem 3‐Chlor‐cycl0penten (Ia) erhält man das Phenoxy‐ Derivat (Ib) und über Epoxide zahlreiche aufgeführte stereoisomere 2‐Amino‐5‐ phenoxycyclopentanole in sterisch einheitlichen Reaktionen.