Bioactive Montanine Derivatives from Halide-induced Rearrangements of Haemanthamine-type Alkaloids. Absolute Configuration by VCD

Abstract

An unexpected rearrangement of haemanthamine-type alkaloids in the presence of halogenating agents has been found. Rearranged compounds present the 5,11-methanomorphantridine framework characteristic of montanine-type alkaloids. These compounds are difficult to obtain because of their scarcity in natural sources and because the synthetic approaches developed so far require numerous steps. Vibrational circular dichroism (VCD) spectroscopy was used to determine the absolute configuration of one of the rearranged compounds. Several rearranged alkaloids showed antimalarial activity.

Recent advances in the use of vibrational chiroptical spectroscopic methods for stereochemical characterization of natural products

“…127 It was also possible to observe that the lowest-energy conformers in both cases showed the N-Me group in the syn orientation. 131 The absolute conguration of the tropane alkaloids 6b-hydroxy-3a-senecioyloxytropane (91), 3a-hydroxy-6b-tigloyloxytropane (92), 3ahydroxy-6b-senecioyloxytropane (93), and 3a-hydroxy-6b-angeloyloxytropane (94), isolated from Schizanthus species, was determined as 1R,3R,5S,6R. 128 The related alkaloids (+)-schizogaline (85), (À)-schizogamine (86), and 6,7-dehydro-19b-hydroxyschizozygine (87), isolated from the same species, had their absolute congurations dened by that of 84 assuming a common biosynthetic pathway.…”

Progress in the Chemistry of Organic Natural Products 100

“…(b) Omit maps through the atoms of water molecule W1. The two H or D atoms have been omitted for the phase calculation (253) Structure Elucidation of Natural Compounds by X-Ray Crystallography Pyrococcus furiosus rubredoxin (283), urate oxidase (284), gamma-chymotrypsin (285), thaumatin (286), and sulfite reductase D (287).…”

“…The Δ 2,4 -compound sorbic acid methyl ester yields the pyrylium ion m/z 111. The EI mass spectra of the double bond isomeric hexenoic acid methyl esters ( 280 ), notwithstanding the characteristic ion m/z 113 for the Δ 2 -isomer, differ in relative abundances of their ions, but with increasing chain length the mass spectra of double-bond isomers assimilate more and more until they become practically indistinguishable ( 283 ).…”

“…Filifolinol (279), isolated from the cuticle of Heliotropium filifolium, together with filifolinyl senecionate (280), belongs to a series of unusual spiro natural products of mixed biogenesis showing the 3H-spiro-1-benzofuran-2,1′-cyclohexane structures (281)(282)(283)(284), which exhibit antibacterial and antiviral activities. The absolute configuration of filifolinol acetate (282) was determined by VCD methodology using DFT at the B3LYP/DGDZVP level of theory (314).…”

Determination of the Absolute Configuration of Natural Product Molecules Using Vibrational Circular Dichroism

“…The first example by Cedrón et al [50] deals with the VCD determination of the AC of a montanine-type alkaloid formed via an unexpected rearrangement of natural hemanthamine-type alkaloids in the presence of halogenating agents. The rearranged product 8 had its structure and relative configuration determined using NMR spectroscopy.…”