β‐Dicarbonyl Compounds as protecting Agents for Amino Groups in Peptides Syntheses

Abstract

reaction conditions. Thus, both y-lactones and &-lactones are obtained from unsaturated, a$-unsaturated esters: e.g. methyl crotonate, gives 72 % 8-valerolactone alongside 20 % P-methyl-y-butyrolactone, white with P,P-dimethylacrylic esters, because of complete isomerization, only P-methyl-&valerolactone is obtained in 88.5 % yield. 20 % 72 % 0 % 88.5 % The unsaturated starting materiaIs can be substituted by alkyl, alkylene, ethoxycarbonyl, and other functional groups. Alicyclic unsaturated carboxylic esters, such as cyclohexenyl, cyclopentenyl, and cycloheptenylisobutyric esters, lead to homologues of iridomyrmecin [ I]. Surprisingly, it was also possible to convert cinnamates into P-phenyl-y-butyrolactone in 34 % yield by employing stoichiometric amounts of the catalyst, although, according to various authors [2], these esters were not susceptible to hydroformylation reactions, giving hydrogenation products only. Publication withheld until now at the express wish of the authors. Received, June 13th. 1962 [Z 359/191 IE] [I J F. Korfe, J. Falbe, and A. Zschocke, Tetrahedron 6,201 (1 959). [2] M . Orchin, Advances in Catalysis 5, 385 (1953); R. Hasek, Organic Chemical Bulletin, 27 (1955) -published by theResearch Laboratories of the Eastman Company.

Studies on lactams. Part 65. N-Unsubstituted .beta.-lactams from .beta.-hydroxy-.alpha.-amino acids. Facile preparation of intermediates for isocephalosporins

“…Caled for CíüHüsNAS: C, 61.36; H, 6.25; N, 7.95. Found: C, 61.55; H, 6.48; N, 7.81. cis-l-[l-[[(p-Nitrobenzyl)oxy]carbonyl]-2-hydroxypropyl]-3-azido-4-styrylazetidin-2-one (13). p-Nitrobenzyl-D-threonine p-toluenesulfonate (9; 34.08 g, 80 mmol) and potassium carbonate (16.56 g, 120 mmol) were suspended in methylene chloride (320 mL) layered with water (160 mL).…”

“…and brine (50 mL), dried (Na2S04), and evaporated to yield 1.50 g of a crude oil. Chromatographic purification of this oil on 100 g of Davison silica gel (100-200 mesh), with chloroform-ethyl acetate (10:5) as eluent, provided the amide 20 (0.580 g, 53.6% yield) as an oil: IR (neat) 3170, 2850, 1750, 1670 cm"1; NMR (CDClg) b 3.85 (s, 3 ), 3.90 (s, 3 ), 4.40 (dd, 2 H, J = 15.0 and 48.0 Hz), 4.50 (s, 2 ), 5.40 (dd, 1 H, J = 5.0 and 9.0 Hz), 5.95 (dd, 1 H, J = 7.5 and 16.0 Hz), 6.60 Hydrogen sulfide was passed through a cooled (0 °C) solution of 13 (18.04 g, 40 mmol) in anhydrous CH2C12 (400 mL) for 20 min. Triethylamine (10.10 g, 100 mmol) in anhydrous CH2C12 (25 mL) was then added dropwise with stirring, and the reaction mixture was maintained at 0 °C for 1 h. The solvent was evaporated, and the residual solid was triturated with benzene (250 mL) and filtered.…”

“…The key compound (13) with various functional groups can be manipulated in a number of ways (Scheme VI) to reach target compounds, such as 19, 23, and 31.…”

Use of Silyl Ester and Enamine Protection for an Efficient Alternate Synthesis of (1S,2S,5R,6S)-2-[(2′S)-(2′-Amino)propionyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Hydrochloride (LY544344·HCl)

“…The utility of silyl groups as temporary protection of carboxylic acid groups and amine protection as an enamine in the form of Dane salts have been well established in the syntheses of peptides, cephalosporins and carbacephs. 3 Therefore, our approach was to incorporate the activation of Dane salt 6, derived from L-alanine, 4 in the form of mixed carboxylic-carbonic anhydride 7 and protection of 1 as silyl ester 9 (Scheme 2). This manuscript describes our efforts that resulted in an efficient synthesis that eliminates the tert-butyl chloride impurity.…”