Study of the stereochemistry, relaxation mechanisms, and internal motions of natural products utilizing proton relaxation parameters: Solution and crystal structures of saxitoxin

It is demonstrated that spin-lattice and cross-relaxation rates of protons are effective and accurate determinants of stereochemistry and internal motion of saxitoxin and hence of natural products in general. Proton relaxation mechanisms are essentially dipolar. Spin-spin analysis of the saxitoxin spectrum gave scalar coupling constants and chemical shifts for all protons. The 3J values for H29, H30, H31, and H32 of the five-membered ring gave interproton distances agreeing within 0.1 Å with those found in the crystal, and the principal side-chain rotamer determined from 3J27,33 and 3J28,34 was that found in the crystal. The double Karplus curve approach used here is a novel approach to R and 5 proton assignment and to determining small-ring stereochemistry. All monoselective, biselective, and nonselective spin-lattice relaxation rates were measured; where monoselective measurements yielded values which still involved cross relaxation, these were corrected to yield true monoselective relaxation rates. The correlation time for each geminal proton vector of the saxitoxin framework was 8.3 X 10-11 s, proving the framework to be rigid. Interproton distances, calculated from cross-relaxation rates, σ, agreed within ±0.2 Å of those found in the crystal and from scalar coupling constants. © 1980, American Chemical Society. All rights reserved.