Nitrogen-containing monoterpene derivatives

#The present invention relates to nitrogen-containing monoterpene derivatives, especially, to novel nitrogen-containing monoterpene derivatives having a pyrindine skeleton synthesized by, for example, substitution of an oxygen atom in a iridoid skeleton for a nitrogen atom.

#Various studies have been directed toward nitrogen-containing monoterpene derivatives having a pyrindine skeleton and processes for synthesizing these derivatives have already been reported. However, none of these processes utilizes the process of this invention wherein an oxygen atom in n iridoid skeleton is replaced with a nitrogen atom. It has been known that iridoid glycosides and aglycones occur in plants, for example, in large amounts in Gardenia jasminoides Ellis, Genipa americana L. etc. of Rubiaceae. It has been said that Gardenia jasminoides Ellis exhibits physiological activities such as purgative, antidotal and antiinflammatory effects and that Genipa americana L. exhibits an antituberculosis effect. The inventors have disclosed that aglycones of irodoid glycosides react with primary amino group-containing substances to form dyestuffs (Japanese Patent Application Nos. 77136/1974 and 130131/1975). However, the chemical structures of components constituting the dyestuffs have not yet been elucidated. The inventors have perfected the present invention upon conducting further investigations on the properties of iridoid glycosides and aglycones thereof and also on the products of reaction of iridoid glycosides or their aglycones with primary amino group-containing substances.

#This invention provides novel nitrogen-containing monoterpene derivatives of general formulae I, II, III, IV and V. This invention further provides polymers as well as substances having various visible absorption characteristics which were produced by dehydrogenative polymerization or oxidation of these novel nitrogen-containing monoterpene derivatives. These compounds can be used not only as mere dyestuff intermediates or dyestuffs themselves but also as reagents for analysis of pharmacological effects of iridoids and pyrindine derivatives, as pharmaceuticals and also as intermediates for the synthesis of useful pyrindine compounds.

#The accompanying drawings show proton nuclear magnetic resonance (PMR), C.sup.13 nuclear magnetic resonance (CMR), infrared absorption (IR), ultraviolet absorption (UV), and visible absorption spectra (VIS) of the novel nitrogen-containing monoterpene derivatives of this invention. FIG. 1-1 shows PMR of a derivative obtained in Example I. FIG. 2-1 shows PMR of a derivative obtained in Example II. FIGS. 3-1, -2, -3, and -4 show PMR, CMR, IR and UV of a derivative obtained in Example III. FIGS. 4-1, -2, -3 and -4 show PMR, CMR, IR and UV of a derivative obtained in Example IV. FIG. 5-1 shows PMR of a derivative obtained in Example V. FIGS. 6-1, -2, and -3 show PMR, IR, and uv of a derivative obtained in Example VI. FIG. 7-1 shows PMR of a derivative obtained in Example VII. FIGS. 8-1, -2, -3 and -4 show PMR, CMR, IR and UV of a compound VIII-2 obtained in Example VIII. FIGS. 8-5, -6, -7 and -8 show PMR, CMR, IR and UV of a compound VIII-3 obtained in Example VIII. FIGS. 9-1 and -2 show PMR and IR of a derivative obtained in Example IX. FIGS. 10-1, -2, -3 and -4 show PMR, CMR, IR and UV of a derivative obtained in Example XI. FIGS. 11-1, -2, -3 and -4 show PMR, CMR, IR and UV of a derivative obtained in Example XII. FIGS. 12-1, -2, -3 and -4 show PMR, CMR, IR and UV of a product XIII-3 obtained in Example XIII. FIGS. 13-1, -2, -3 and -4 show PMR, IR, UV and VIS of a derivative obtained in Example XVII. FIGS. 14-1, -2, -3, -4 and -5 show PMR, CMR, IR, UV and VIS of a derivative obtained in Example XVIII .

#A mixture of 452 mg of genipin and 0.5 ml or 28% aqueous ammonia was dissolved in 40 ml. of a mixture of McIlvaine buffer solution (pH 7.2) and ethanol (1:1). After heating the mixture at 70.degree. C. under argon, the solvent was evaporated under reduced pressure and the residue was subjected to extraction with CHCl.sub.3 (50 ml..times.3). The CHCl.sub.3 extract was washed with water and then the solvent was evaporated under reduced pressure to yield 430 mg of a colorless syrupy residue.

#The residue was purified on a silica gel column with ether as the developing solvent. Eluate was fractionated and the solvent was evaporated under reduced pressure to yield colorless needles. The structural formula of this compound is as follows: ##STR13## PMR: FIG. 1-1 MS (Mass spectrum parent peak) m/e 189

#A mixture of 452 mg (2 mM) of genipin and 402 mg (6 mM) of methylamine hydrochloride was dissolved in 40 ml. of a mixture of McIlvaine buffer solution (pH 7.2) and ethanol (1:1). After stirring at room temperature under argon for 4 hours, the reaction mixture was extracted with chloroform. Evaporation of the solvent yielded 420 mg of a red oily substance.