Base-catalysed double-bond isomerization offers a convenient, high-yield route to a variety of new cannabinoids, as well as to compounds of this group which are accessible with some difficulty. By this route w e have obtained optically active A2-tetrahydrocannabinols and A3-tetrahydrocannabinols, the A6-isomer of cannabidiol, and other novel cannabinoids.The reactions of cannabinoids with acids have been investigated in considerable detail as befits the terpenoid nature of this class of compounds.'*2 By contrast only a few reactions proceeding through cannabinoid anions have been r e p ~r t e d . ~. ~ The application of one of these reactions, which was reported by Fahrenholtz et a1.: is of considerable importance. It allows the conversion of the easily prepared A'-tetrahydrocannabinol (A6-THC) (la) into A'-THC (2a) by the addition of the elements of hydrochloric acid across the double bond of A6-THC (la) to yield (3), followed by dehydrohalogenation initiated by the adjacent phenoxide ion formed by a strong base.5We report now that by base-promoted anionic isomerizations it is feasible to obtain numerous isomers of natural cannabinoids some of which were hitherto unknown.Two procedures were followed for the production of cannabinoid anions: A, t-pentyl potassium in toluene-hexamethylphosphoric triamide (HMPA) (6: 1) at reflux temperature, and B, n-butyl-lithium solution in hexane ( 1 . 6 5 ~) admixed with HMPA at 0 "C. These procedures were established after considerable experimentation (see Experimental section) with other solvent systems. HMPA was found to be indispensable for the isomerizations described below.A'-THC (2a).-Under the conditions of procedure B, A1-THC (2a) produces an 8.1 mixture of (lS,4R)-A2-THC (4a), m.p. 153-154 "C, and (1R,4R)-A2-THC @a), m.p. 54-55 "C. Procedure A leads to a 1 :9 mixture of (4a) to (54 respectively.

Structural and kinetic features of the TATA box located in the center of the alternating self-complementary d(C-G-C-G-T-A-T-A-C-G-C-G) duplex (TATA 12-mer) and d(C-G-C-G-C-G-T-A-T-A-C-G-C-G-C-G) duplex (TATA 16-mer) have been probed by high-resolution proton and phosphorus NMR spectroscopy in aqueous solution. The imino exchangeable Watson-Crick protons and the nonexchangeable base protons in the TATA box of the TATA 12-mer and TATA 16-mer duplexes have been assigned from intra and inter base pair nuclear Overhauser effect (NOE) measurements. Imino proton line-width and hydrogen exchange saturation recovery measurements demonstrate that the dA X dT base pairs in the TATA box located in the center of the TATA 12-mer and TATA 16-mer duplexes are kinetically more labile than flanking dG X dC base pairs. The proton and phosphorus NMR parameters of the TATA 12-mer monitor a cooperative premelting transition in the TATA box prior to the onset of the melting transition to unstacked strands. Phosphorus NMR studies have been unable to detect any indication of a right-handed B DNA to a left-handed Z DNA transition for the TATA 12-mer duplex in saturated NaCl solution. By contrast, we do detect the onset of the B to Z transition for the TATA 16-mer in saturated NaCl solution. Proton and phosphorus NMR studies demonstrate formation of a loop conformation with chain reversal at the TATA segment for the TATA 12-mer and TATA 16-mer duplexes on lowering the DNA and counterion concentration. The imino protons (10-11 ppm) and phosphorus resonances (3.5-4.0 ppm; 4.5-5.0 ppm) of the loop segment fall in spectral windows well resolved from the corresponding markers in fully paired segments so tha it should be possible to identify loops in longer DNA helixes. The equilibrium between the loop and fully paired duplex conformations of the TATA 12-mer and TATA 16-mer is shifted toward the latter on addition of moderate salt.

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