New Constrained Amines in a Bicyclo[2.2.1]Heptane Skeleton

Abstract

In this paper we present an efficient procedure for obtaining ether-protected bicyclo[2.2.1]heptane amines in six steps, from an optically active keto-alcohol norbornane compound, for building the heterocyclic bases of pyrimidine and purine constrained nucleosides. Trityl as protecting group makes it possible to isolate 5-endo-compounds in pure form by selective crystallization, and to isolate the intermediates in the next 3 steps of the reaction by crystallization. With TBDMS, all compounds were obtained as oil. The direct selective reduction of the keto-alcohol norbornane compound gave the pure 5-endo-diol 4d in high yield, which was then selectively protected at the primary hydroxyl with a trityl group; the next steps are similar for obtaining the trityl-protected bicyclo[2.2.1]heptane amine. The azide intermediates are valuable intermediates for click chemistry.

Trifluoroacetylation of Alcohols During NMR Study of Compounds with Bicyclo[2.2.1]heptane, Oxabicyclo[3.3.0]octane and Bicyclo[3.3.0]octane Skeleton

“…A comparison of 1 H and 13 C-NMR spectra of the starting compound 1a and the esterified compound 1b is presented in Figure 2. Starting from this observation, the exo-azide compound 2a was similarly studied by addition of TFA in NMR tube, and the esterification to 2b was also finished in 24 h (Figure 3 13 C-NMR spectra in CDCl3 of endo-azide 2a and that of the esterified compound 2b, formed in 24 h by addition of TFA Then the study was extended to other compounds with primary alcohol groups (3a-7a), with primary and secondary alcohol groups (8a-12a), a secondary alcohol group alone (13) and a secondary alcohol group in the presence of a secondary allylic alcohol (14)(15), in racemic: 5a, 10a-12a, or optically active form: 1a-4a, 6a-9a, 13-15, usually used in our laboratory, presented in Figure 1, which contain:…”

“…-a bicyclo[3.3.0]octane triol containing two primary alcohol groups and a secondary alcohol group linked to C5 carbon atom (compounds 11a) or to C6 carbon atom (12a, with a primary alcohol protected as acetate). -an enone (13) and two diols (14,15) in prostaglandin intermediate, containing a double bond.…”

“…1.NMR spectra of the compound 1a and of the trifluoro acetylated compound 1b. [13][14][15] 13 Compound (±)-5a: 1 H-NMR-500 MHz (CDCl3, δ ppm, J Hz): 3.98 (dd, 1H, H-2, 3.7, 7.9), 3.93-3.85 (m, 4H, OCH2CH2O), 3.80 (dd, 1H, 6.7, 12.0), 3.78 (dd, 1H, 6.6, 12.0), 2.50 (dd, 1H, H-3, 8.0, 13.9), 2.49 (d, 1H, H-1, 6.6), 2.30 (dd, 1H, H-7, 6.6, 6.7), 2.22 (d, 1H, H-4, 4.1), 1.96 (dt, 1H, H-6, 5.5, 13.9), 1.94 (m, 1H, H-3), 1.92 (s, 1H, H-OH), 1.48 (d, 1H, H-6, 13.9), 13 13 Compound 8a: 1 H-NMR-500 MHz (CDCl3, δ ppm, J Hz): 4.23 (dt, 1H, H-5, 3.5, 9.9), 4.03 (dd, 1H, H-2, 3.6, 8.0), 3.96 (dd, 1H, H-8, 7.8, 11.4), 3.91 (dd, 1H, H-8, 6.5, 11.4), 2.79 (dd, 1H, H-3, 8.0, 14.6), 2.46 (d, 1H, H-1, 5.0), 2.39 (t, 1H, H-4, 4.1), 2.14 (ddd, 1H, H-6, 5.2, 9.9, 13.7), 2.00 (t, 1H, H-7, 7.9), 1.96 (brt, 1H, H-3, 3.6, 14.6), 1.59 (s, 2H, OH), 0.91 (dd, 1H, H-6, 3.0, 13.7), 13 10.NMR spectra of the ent-Corey compound 10a and of the bis-trifluoroacetylated compound 10b. 13 12.NMR spectra of the optically active diol compound 14a and of the bis-trifluoroacetylated compound 14c.…”

New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety

“…In our previous papers [33,34,35,36,37,38] we used an optically active bicyclo[2.2.1]heptane scaffold to obtain a library of L-type carbocyclic nucleosides X and tested them for antiviral and anticancer activity (Figure 3). Compounds Xa and Xb were “the most prospective for their antiviral activity against influenza virus due to their low toxicity and high activity” [35].…”