Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

Summary A unified strategy was followed for the synthesis of three putrescine bisamides, (+)-grandiamide D, dasyclamide and gigantamide A, isolated from leaves of Aglaia gigantea, by making use of a common synthetic intermediate prepared by the Baylis–Hillman reaction. Asymmetric synthesis of the natural (+)-grandiamide D was accomplished from camphor sultam.

(c g/100 mL, in solvent). Reactions that required inert atmosphere and moisture control were carried out in a nitrogen atmosphere employing oven-dried glassware. All the solvents were used as purchased. All the chemicals were purchased from commercial sources. s3
Spectral data for compound 13 was in agreement with the values reported in the literature [1].
Spectral data for compound 14 was in agreement with the values reported in the literature [2].

Synthesis of N-(4-aminobutyl)cinnamamide (11) [3]
A solution of tert-butyl 4-cinnamamidobutylcarbamate (10, 18.00 g) in EtOH (180 mL) was treated with 6 N HCl (90 mL) and the mixture was stirred at 50 °C for 3 h. The EtOH s7 was distilled off and the residue was basified 2 N NaOH solution to pH 14 and extracted with DCM (4 x 100 mL). The combined organic layer was dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure to provide the title compound 11 as pale brown solid.
Yield: 11.00 g (89%) Spectral data for compound 11 was in agreement with the values reported in the literature [3].
Yield: 1.10 g (75%) Spectral data for compound 5 was in agreement with the values reported in the literature [4].

17
The ester (+)-16 was hydrolyzed with LiOH as described earlier in the synthesis of compound (±)-17 to afford the title compound (+)-17 as pale yellow oil.

Synthesis of gigantamide A (7) [4]
To a solution of dasyclamide (6, 100 mg, 0.0003345 mol) in a mixture of DMSO (1 mL) and CHCl 3 (2 mL), at 0 °C, was added pyridinium chlorochromate (180 mg, 0.000836 mol) in one lot. The orange solution was warmed to room temperature and stirred for 20 h. The reaction mixture was poured into a mixture of 1 N HCl (5 mL) and CHCl 3 (10 mL). The organic layer was separated, washed with water (2 x 25 mL), brine (10 mL), dried over Na 2 SO 4 and concentrated under reduced pressure to brown solid. Purification by preparative TLC, using CHCl 3 /MeOH (9/1) as solvent system, afforded three