Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives

Abstract

A selective synthesis of 7‐ or 14‐nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α‐hydroxy‐15,16‐dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3‐nitroaniline, 3‐(trifluoromethyl)aniline, and 4‐(trifluoromethyl)aniline yield the subsequent 7α‐, 7β‐ and 14αnitrogen‐containing diterpenoids. The reaction with 2‐nitroaniline, 4‐nitro‐2‐chloroaniline, 4‐methoxy‐2‐nitroaniline, phenylsulfamide, or tert‐butyl carbamate proceeds with the formation of 7α‐nitrogen‐substituted diterpenoids as the main products.

Synthesis of Macrocyclic Peptide-Diterpenoid Conjugates by a Sequential Arylation/Peptide Coupling/Click Macrocyclization Procedure

“…General methods 1 Н and 13 C NMR spectra were registered on Bruker AV-400 ( 1 H: 400.13 MHz, 13 C: 100.61 MHz), Bruker AV-300 ( 1 H: 300.13 Mz, 13 C: 75.47 MHz), Bruker AV-600 ( 1 H: 600.30 MHz, 13 C: 150.95 MHz) (Bruker BioSpin GmbH, Rheinstetten, Germany) instruments. Deuterochloroform (CDCl 3 ) was used as a solvent, with residual CHCl 3 (δ H = 7.24 ppm) or CDCl 3 (δ C = 77.0 ppm).…”

“…Deuterochloroform (CDCl 3 ) was used as a solvent, with residual CHCl 3 (δ H = 7.24 ppm) or CDCl 3 (δ C = 77.0 ppm). In the description of the 1 H and 13 C NMR spectra, the atoms numeration system given in macrocycle 11 was used. The IR spectra were recorded by means of the KBr pellet (or film) technique on a Bruker Vector-22 spectrometer.…”

“…[33] 1-Azido-2-iodobenzene 2 was synthesized by reported method. [34] In the NMR 1 H and 13 С spectra the assignments marked with the same symbols *, # are interchangeable. Synthesis of compounds 9a-d. Glycine (1.00 g, 13.3 mmol) or L-valine (1.56 g, 13.3 mmol) was dissolved in a mixed solvent of potassium hydroxide aqueous solution and 1,4-dioxane (40 mL, 1:1 V/V).…”

“…The performed synthetic transformations of isopimaric acid indicate the possibility of carrying out the transformation along the path of complication of the initial molecule with high stereochemical control. [12][13][14][15][16][17][18] As oligopeptides, we used dipeptides containing the amino acid residues of valine and glycine. The choice of the latter is determined both for revealing the effect of steric factors on the yield of target macrocyclic products and data on the perspective biological activity of compounds containing them.…”

Recent Developments in Asymmetric Allylic Amination Reactions

“…For example, gold(III) chloride efficiently catalyzes the amination of the isopimaric acid derivative 285 with 2-nitroaniline to afford allylic amine 286 in 90% yield, in addition to a trace amount of a dehydrated by-product (Equation 23). 173 A striking feature with this process is that the selectivity of the reaction is specific to 2-nitroaniline, since various other nitro-, haloand acetyl-substituted anilines provide significantly lower regio-and diastereospecificity, in addition to lower yields because of competitive dehydration and Friedel-Crafts type allylic arylation reactions.…”