Notes- A Novel Ring System: 3,8-Diazabicyclo[3.2.1]octane

!-Substituted 2,5-Bischloromethylpyrrolidines. A New Class of Adrenolytic Agents

“…In addition to the desired heterocyclic esters and diesters (II), a number of by-products were obtained whose isolation and characterization are the subject of another communication. 5 Lithium aluminium hydride reduction of II yielded the expected mono-and biscarbinols (III) which were converted to the hydrochlorides of the corresponding chloromethyl derivatives (IV) by means of thionyl chloride. The preparation of several bischloromethylpyrrolidines (IV; = 2) has been reported recently by Cignarella and Nathansohn.6 A number of the mono-and bischloromethylpyrrolidine derivatives (IV; = 2) exhibited an anomalous melting point behaviour (liquefaction followed by rapid resolidification) which may be indicative of thermal rearrangement via an ethylenimmonium intermediate.…”

“…Additional comparative studies for adrenolytic activity were performed in cats with Dibenamine and phenoxybenzamine as reference drugs. 1-Substituted pyrrolidines substituted by a single chloromethyl group (ERL-551, 548 and 547) were rather weak adrenolytic agents, inhibiting the pressor response of epinephrine in intravenous amounts of 5 mg/kg or more.…”

Analogs and Homologs of Proline and Hydroxyproline

“…207°, was synthesized via diethyl 2-methyl-A1-pyrroline-5,5-dicarboxylate (LXXX) as follows (217). (iv) 5-Methylproline inhibited actinomycin production in Streptomyces antibioticus less than either 3or 4methylproline (296) ;CH-T"1 -n-Propyl• and 4-(J-methyl-2-ethoxy ethyl) proline were prepared by route iv above from the appropriate 1- Derivatives of m-5-carboxyproIine (pyrrolidine 2,5dicarboxylic acid) have been used extensively (49)(50)(51)(52)218) in the synthesis of 3,8-diazabicycIo [3.2.1 ]octanes, which is illustrated by the following synthesis (49). During cyclization of amido esters the trans isomer of the starting material was sometimes isolated as a side product (52).…”

“…6-Carboxyproline Derivatives Derivatives of cis-5-carboxyproline (pyrrolidine 2,5-dicarboxylic acid) have been used extensively (49)(50)(51)(52)218) in the synthesis of 3,8-diazabicyclo [3.2.l]octanes, which is illustrated by the following synthesis (49).…”