Bicyclic lactams as templates for peptidomimetics. Studies on stereoselective synthetic routes to 6-oxoperhydropyrrolo[1,2-a]pyrazines

5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-Based Potent and Selective CCK1 Receptor Antagonists: Structure−Activity Relationship Studies on the Central 1,3-Dioxoperhydropyrido[1,2-c]pyrimidine Scaffold

“…Then, sequential N -Boc removal and coupling with Boc- l -Trp-OH provided a (5:1) diastereoisomeric mixture of the 1-thioxo analogues 5a and 5b , which were chromatographically resolved. Reduction of 3 with nickel boride, generated in situ from NiCl 2 ·6H 2 O and NaBH 4 in a (1:1) THF-MeOH mixture, − led to the 3-oxoperhydropyrido[1,2- c ]pyrimidine derivatives 4 , whose N -Boc removal followed by coupling with Boc- l -Trp-OH, and chromatographic separation yielded the 1-reduced analogues 6a and 6b . On the other hand, thionation of the 3-oxo-1-thioxoperhydropyrido[1,2- c ]pyrimidines 3 with Lawesson's reagent − led to the 1,3-dithioxo derivatives 7 , and the following N -Boc removal and coupling with Boc- l -Trp-OH provided the corresponding 5-(Boc-tryptophyl)amino derivatives 8a and 8b .…”

Functionalized Cis- and Trans-Fused Bicyclic α-Amino Acids via Stereoselective Double Annulation and Dequaternization Reactions

“…This reasoning led us to reduce the amide moiety of 17a (Scheme 9). Treatment of 17a with Lawesson's reagent gave the thioamide 19 in 94% yield, and reductive desulfurization of 19 by nickel boride gave amine 20 in 80% yield . (One-step reduction of 17a to 20 with BH 3 gave an unsatisfactory yield.)…”

“…The electron-withdrawing CO 2 R group, though, was expected to render this ethynyl ketone exceedingly unstable. We chose to mask the CO 2 R group as a p -methoxyphenyl ( p -anisyl, An) group for three reasons: (1) p -anisyl ethynyl ketone ( 1 ) was known and stable, (2) the An group was expected to be stable to catalytic hydrogenation and to strong acid, our two methods for azacyclization, and (3) the An group could be converted to a CO 2 H group under conditions (excess NaIO 4 , catalytic RuCl 3 ·H 2 O) that did not generally affect amides, esters, nitriles, or unfunctionalized C−C and C−H σ bonds. , …”

Efficient Syntheses of Polyamines Bearing 1H-Tetrazol-5-yl Units on Their Amino Functions

“…We then followed an alternative route, which involved the conversion of the amide to the corresponding thioamide by treatment with Lawesson's reagent, followed by reduction under mild reduction conditions, using the system sodium borohydride/nickel(II) chloride hexahydrate. 8 Indeed, thionation of the amides 11 and 12 with Lawesson's reagent in tetrahydrofuran at ambient temperature produced the corresponding thioamides 13 and 14 in 60% and 55% yields, respectively. These compounds were then reacted with sodium borohydride/nickel(II) chloride hexahydrate in methanol-tetrahydrofuran 1:1 to give the expected amines 15 and 16 in 62% and 65% yields, respectively.…”