TOXIC PRINCIPLES OFHIPPOMANE MANCINELLA

Abstract

IThe alcoholic extract of the leaves and twigs of Hippomane mancinella L. was separated first into two toxic fractions: the water-soluble ( A ) and the ether-soluble (B). Chromatography of ( A ) gave fractions A1-A,, all of which were purified and characterized. Al was found to be 2-hydroxy-4,6-dimethoxyacetophenone. Fraction A, was shown t o be ellagic acid while A2-A, were its tri-, di-and monomethyl ethers respectively. A6 and A, were found to be the toxic principles of the aqueous ( A ) fraction and were named hippomanins B and A respectively. Of these, the major component, hippomanin A was obtained as a pale yellow crystalline solid of molecular formula C27H2201e. Hippomane mancinella L. ( N . 0. Euphorbiaceae), commonly called manchineel, has enjoyed the reputation of being one of the most toxic plants in the Caribbean region for many centuries. LAUTER, FOX and ARIAIL (1952) who reviewed the literature u p to 1952 described in detail the toxic manifestations which result from physical contact and ingestion of parts of the plant. It appears that the sap from this medium-sized tree causes a reaction characteristic of a burn and contact with eyes produces severe conjuctivitis which, if complicated by secondary infection could result in loss of sight.'. In spite of such reputation, there have been relatively few studies on the nature of the toxic principles of this plant. SCHAEFFER, LAUTER and FOOTE (1954) described the isolation of the known 2-hydro-4,6-dimethoxy-acetophenone and a carotenoid substance from the leaves of the plant. T h e fruits were reported to contain a water-soluble compound, very sensitive to oxygen and qualitative tests suggested the presence of physostigrnine (LAUTER and FOOTE, 1955). In a more recent study, DORAN (1967) reported the isolation of a C 32 hydrocarbon from -In the author's own experience, contact with the latex on the chin for two minutes caused severe burning sensation around the nasal and oral regions, profuse salivation, loss of sensation of taste and nasal irritation for nearly three hours. Even a minor contact in the eye caused severe burning and irritation for nearly 9 hours.

In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis

“…Hippomanin A, an ellagitannin found in Hippomane mancinella L. is known for its toxic properties. It causes oropharyngeal and gastrointestinal tract lesions, hypotension and bradycardia 90,91 . Here, Hippomannin A recorded − 9.6 BE and forms H bond with ARG553, TYR619, ARG624, THR680, SER682 and ASP760 with target site of RdRp.…”

Strategies for the Synthesis of Ellagitannins

“…87 We were able to isolate the perbenzylated precursors of the natural products gemin D (106) (68% theoretical yield) and hippomanin A (108) (66% theoretical yield), each with an S-configured biaryl component, as the only cyclic products. Finally, the ellagitannins gemin D (84) 90,143,144,165,166 and hippomanin A (85) 90,145,146,166,167 were obtained by complete debenzylation with Pd-C/H 2 (Scheme 24). The spectroscopic data of synthetic 84 agreed in all respects with those of natural 84.…”

“…Total Syntheses of Gemin D (84) and Hippomanin A (85); Investigation of Phase-Transfer-Catalyzed Monobenzylation ReactionsThe isolation of gemin D (84) from the leaves of Geum japonicum (Rosa-ceae) and from the flowers of Camellia japonica (Theaceae) was first reported143 in 1982, with the full characterization of 84 being published in 1985 by Okuda et al144 The isolation of hippomanin A (85) from the aerial parts of Hippomane manci-nella L. (N. O. Euphorbiaceae) had already been reported in 1974 by Rao,145 but the structure elucidation of 85 was only reported three years later146 (Figure 5). Both gemin D (84) and hippomanin A (85) possess an S-configured HHDP unit linked to the 4,6-positions of D-glucopyranose.…”

Exploring structurally diverse plant secondary metabolites as a potential source of drug targeting different molecular mechanisms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pathogenesis: An in silico approach

“…It causes oropharyngeal and gastrointestinal tract lesions, hypotension and bradycardia (Boucaud-Maiter et al, 2019;Rao, 1974). Here, Hippomannin A recorded -9.6 BE and forms H bond with ARG553, TYR619, ARG624, THR680, SER682 and ASP760 with target site of RdRp.…”