Cryptospirolepine, a Unique Spiro-nonacyclic Alkaloid Isolated from Cryptolepis sanguinolenta

Abstract

From the alkaloidal fractions of the West African plant Cryptolepis sanguinolenta (Asclepiadaceae), two alkaloids were purified: one was identified as the known indoloquinoline alkaloid cryptolepine [1], A second, novel alkaloid was shown to have an empirical formula of C34H24N4O based on exact mass measurement. Through the concerted application of a series of homonuclear and inverse-detected 2D nmr experiments, the structure of the second alkaloid was established as a spiro-nonacyclic alkaloid, cryptospirolepine. One portion of the structure of cryptospirolepine [2] may be biogenetically derived from cryptolepine [1],Cryptolepis sanguinolenta (Lindl.) Schlechter (Asclepiadaceae), a shrub indigenous to West Africa, has long been employed by Ghanaian traditional healers in the treatment of various fevers, including malaria (1). A root decoction has been used in the clinical therapy both of malaria and of urinary and upper respiratory tract infections by Oku Ampofo at the Centre for Scientific Research into Plant Medicine in Ghana since 1974 (1). The indoloquinoline alkaloid cryptolepine (5-methyl-5H-indolo-[3,2-¿}quinoline) [1] was first isolated from extracts of the roots of Cryptolepis triangularis N. E.Br., a species native to the Belgian Congo, by Clinquart in 1929 (2). Shortly thereafter, the alkaloid was again isolated from the same species by Delvaux (3). Quite paradoxically, cryptolepine had been synthesized some 20 years prior by Fichter and coworkers (4-6). Cryptolepine was isolated from a Nigerian sample of Cr. sanguinolenta in 1951 by Gellert et al. (7). Almost 30 years later, the alkaloid was isolated from a

Phytochemical content of leaf and stem of Marsilea quadrifolia (L.)

“…Flavonoids and lavones are widely distributed secondary metabolites with antioxidant and antiradical properties [57]. The alkaloid extracts obtained from medicinal plant species have multiplicity of host-mediated biological activities, including antimalarial, antimicrobial, antihyperglycemic, anti-in lammatory and pharmacological effects [58].…”

Quindolinocryptotackieine: the elucidation of a novel indoloquinoline alkaloid structure through the use of computer‐assisted structure elucidation and 2D NMR

“…7 is assigned as the structure. The alkaloid is a complex mixed dimer comprised of cryptotackieine (top) and quindoline (bottom), to which we give the name quindolinocryptotackieine (10). Both of the component alkaloid substructures are known from C. sanguinolenta and moreover quindoline was isolated and characterized prior to the acquisition of these data; cryptotackieine was isolated and characterized from the same extract of the plant a number of years after the acquisition of the data for TC-6.…”

“…3,4 The isolation and structural characterization of numerous new members of the indoloquinoline family of alkaloids has been reported in the intervening years. Variations in the ring fusion of the indoloquinoline nucleus have been found; 5,6 several indolobenzazepines have been reported: 7,8 some dimeric structures including cryptomisrine (1), 9 biscryptolepine (2) 6 and cryptoquindoline (3) 8 have been isolated and characterized along with more complex systems that include cryptospirolepine 10 and cryptolepicarboline (4), 11 the latter being a mixed dimer all of the available data was not assembled in 1991-92 when these data were first examined.…”

“…Consequently, dimeric structures were not considered as a possibility. Next, the acquisition of the TC-6 data immediately followed the structural characterization of the complex spiro nonacyclic alkaloid cryptospirolepine 10 also probably serving to bias our thinking away from simpler dimeric structures, particularly in the light of the problematic mass spectral data then available. Third, there are several carbon resonances that are remote from the nearest proton in the TC-6 structure, which precluded long-range heteronuclear correlation responses for these resonances.…”

Perturbations of15N chemical shifts followingN-oxidation of the alkaloid cryptolepinone determined by1H-15N GHSQC and GHMBC at natural abundance

“…15,16 The development of gradient-enhanced variants of the HMQC and HMBC17 experiments (variously known as GE-HXQC or GHXQC, where X may be either M for multiple quantum or S for single quantum, and GE-HMBC or GHMBC, respectively) followed and were the topic of a very thorough treatment by RuizCabello et al 18 The Ðrst application of gradient inversedetected heteronuclear shift correlation experiments to alkaloids of which we are aware was the 1993 presentation of Koshino and co-workers applying the technique to nicotine and strychnine19 and published in 1995. 20 The availability of gradient long-range 1HÈ15N techniques has sparked considerable interest in applications to alkaloids.…”