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The 14C-labeling pattern in aloenin (I) biosynthesized from [2-14C]malonate, [1-14C]acetate, [1-14C]- and [3-14C]phenylalanine, and [methyl- 14C]methionine in Aloe arborescensMill. var. natalensisBerger demonstrated that the carbon skeleton of aloenin is generated by the acetate-malonate pathway and that the methyl of the methoxyl group is originated from methionine.

The structure of aloenin, a bitter glucoside from Aloespecies, has been reinvestigated and elucidated to be 6-(2′-β-d-glucopyranosyloxy-4′-hydroxy-6′-methyl)phenyl-4-methoxy-2-pyrone (2) by a combination of the chemical and spectroscopic methods.

The structure of alnuserrudiolone, a new C31-dammarane-type triterpene isolated from the male flowers of Alnus serrulatoidesCall. (Betulaceae), has been elucidated to be (20s)-12ß,20-dihydroxy-24-methylene-dammaran-3-one (I) by a combination of chemical and spectroscopic methods.

U-14C-l-Leucine and 4,5-3H-l-leucine were incorporated into linalool (I) in Cinnamomum CamphoraSieb. var. linalooliferumFujita in 0.004% yield at the highest value. Its labeling patterns have indicated that DMAPP may originate not only from mevalonic acid but also from leucine not via the acid.

Sodium [2-14C]malonate and d-[U-14C]glucose were incorporated into protoanemonin (I) in Ranunculus glaberMakino in 0.60 and 0.09% yield respectively at the highest value. Its labeling pattern suggests that the lactone I is biosynthesized by the condensation of glycerate and malonate in a terrestrial part of the plant.

A new bitter glucoside, named aloenin, isolated from Aloespecies has been established to be 2-(carbomethoxymethyliden)-4-(ß-d-glucopyranosyloxy)-7-hydroxy-5-methylchromene (1). This is an unique example of naturally occurring chromene having the carbomethoxymethylidene group on C-2.

The incubation of terminally modified squalene 2,3-oxide analogs with the enzyme preparation of hog liver yielded the corresponding lanosterol analogs, respectively, at different conversion rates. The interaction of 2,3-oxidosqualene cyclase with the substrates has thus been found to be influenced by the bulk of the terminal moiety.

The conformational analysis of a stereoisomeric pair of 4-hydroxymenthones, (1R:4R)-(-)-4-hydroxymenthone (1) and (1R:4S)-(+)-4-hydroxyisomenthone (2), was made by means of temperature-dependent circular dichroism. It was demonstrated that a-hydroxyketone (1) exists in the conformational equilibrium: 1a\leftrightarrows1b; the conformer 1aexists predominantly in a nonpolar medium, whereas the conformer 1bis more stable than 1ain a polar medium. On the other hand, the other isomer, (2), exists preferentially in the state of the conformer 2bin either a polar or a nonpolar solvent. The results were interpreted in terms of the competition of the steric factor and intramolecular hydrogen-bonding.

In connection with the bromination of 3-acetoxy-pin-2-ene (II), the acid-catalyzed rearrangement of 2α-bromo-10β-pinan-3-one (I) was investigated under several conditions. The bromoketone (I) was thus found to yield (+)-6-endo-bromocamphor (III), (−)-α-carvone (V), (−)-8-hydroxycarvotanacetone (VI), carvacrol (VII), (+)-dihydro-β-campholenolactone (VIII), and (+)-campholenic acid (IX). It also became clear that the bromocamphor (III) and the (V), (VI), and (VII) products are directly formed from the bromoketone (I), whereas the γ-lactone (VIII) is obtained viaα-campholenic acid (IX) from the bromocamphor (III). The mechanistic implications of the rearrangements are discussed.

The stereochemical structure of (+)-2-hydroxypinocamphone (II), which was obtained from (-)-a-pinene (I) by the permanganate oxidation, was examined by a combination of physicochemical methods. It was thus found that the C-2 methyl group is trans with respect to the C-6 bridge and that the preferred conformation is V having an axial hydroxyl group. In addition, the preferred conformation of cis-a-pinene glycol (IX) and trans-a-pinene glycol (X), which were produced from II by the lithium aluminum hydride reduction, was found to be IXa and Xa respectively.

The preferred rotational conformation of the acetyl group of (+)-10-nor-8-oxoneomenthol (I), (-)-10-nor-8-oxomenthol (II), (-)-10-nor-8-oxocarvomenthol (III), and (+)-10-nor-8-oxoneocarvomenthol (IV) has been examined by acombination of conformational analysis by a prioricalculation and variable-temperature circular dichroism and infrared spectrum measurements. Compound I exhibited an inversion in the sign of the Cotton effect upon a change in the solvent. This phenomenon was interpreted as indicating the conformational change Ia\ightleftarrowsIb. The cause of the change was ascribed to the formation and subsequent rupture of the intramolecular hydrogen bond. Compound II exhibited a solvent-depending circular dichroism curve similar to the curve of I; this was explained as indicating the existence of a conformational equilibrium between the free conformer, IIa, and the internally-hydrogen-bonded conformers, IIb, IIc, and IId. Furthermore, compounds III and IV were found to take preferentially the IIIa–IIIb and IVa–IVb conformations respectively.

1-Hydroxy-p-menth-3-en-2-one (1) was prepared from α-terpinene by the t-butyl chromate oxidation, trans- and cis-p-Menth-3-ene-1,2-diols (4 and 5), 1-hydroxyisocarvomenthone (2), and 1-hydroxycarvomenthone (3) were also prepared from the compound 1 by lithium aluminum hydride reduction or by hydrogenation. The configurations of these compounds, 1–5, were identified on the basis of chemical evidence, and then the preferred conformation was determined by infrared spectroscopy on the basis of the conception of intramolecular hydrogen bonding. 1 and 2 were found to exist predominantly in the hydrogen-bonded conformations, 1a and 2a, respectively. With respect to 3, the existence of the conformational equilibrium, 3a\ightleftharpoons3b, was demonstrated by the presence of the free and bonded hydroxyl bands. Moreover, 4 and 5 were proved to take the preferred conformations of 4a and 5a respectively.

The results obtained in the preceding papers (Parts I–III) of this series showed that, on oxidation with t-butyl chromate, the primary alcohol without a p-electron system on the carbon a to the hydroxymethyl group yields the corresponding ester in a comparable yield, together with the aldehyde and the acid, and also that the cyclic a-glycol with two secondary hydroxyl groups affords the corresponding cyclic ester, along with the glycol fission product. Chemical examination and infrared spectroscopic study have now proved that the course of the formation of these esters does not follow the direct esterification of the alcohol with the acid formed from it by oxidation, but rather involves the formation of a hemiacetal intermediate between the original alcohol and the aldehyde produced from the alcohol, and the subsequent oxidation of the hemiacetal. The oxidation of alcohols with t-butyl chromate has also been discussed generally on the basis of the results of our previous papers and of the present work.

The oxidation with t-butyl chromate has been carried out with benzyl alcohol, its p-substituted derivatives and trans-cinnamyl alcohol, and also with ß-phenylethyl alcohol. In the former alcohols, the corresponding aldehyde was obtained as the main product, but the corresponding ester was not formed. On the other hand, the latter alcohol, containing a methylene group adjacent to the hydroxymethyl group, produced the corresponding ester, aldehyde and acid, as in the case of a saturated primary aliphatic alcohol.

The conformational analysis of (+)-p-menthane-3,4-diol, which had been obtained by the hydroxylation of (+)-p-menth-3-ene with performic acid in the presence of water, has been performed mainly by means of infrared spectra. It has been shown that the two hydroxyl groups at the C3- and C4-positions take a diaxial conformation, that they are, accordingly, trans to each other, and that the methyl group presumably holds an equatorial orientation. It has also been found that p-menthane-trans(diaxial)-2,3-diol results from the p-menth-2-ene coexisting in the sample of p-menth-3-ene. A stereochemical course of the hydroxylation reaction has been discussed.

The stereochemistry of (+)-dihydro-β-campholenolactone (II) and (−)-1,2-campholide (III) was clarified to be Ila and IVc, respectively, by a combination of nuclear magnetic resonance, optical rotatory dispersion and circular dichroism measurements.

The labelling pattern in geraniol biosynthesized from [2-14C]mevalonic acid in leaves of Pelargonium roseumBourbon was consistent with the pathway shown in the scheme. The radioactivities at C-4 and C-8 (and/or C-10) were unbalanced, in opposition to the results observed for geraniol biosynthesized in flowers of the rose.

The conformations of (1R:4R)-(−)-p-menth-8-en-2-one (1) and of diastereoisomeric pairs of (+)-1-hydroxy-p-menth-8-en-2-one, (2) and (3), (+)-1-hydroxy-p-menthan-2-one, (6) and (7), and (+)-1-hydroxy-8-bromo-p-menthan-2-one, (10) and (11), were examined by a combination of infrared spectra and temperature-dependent circular-dichroism (CD). Explanations are given mainly with regard to the epimeric pair, (2) and (3). It is demonstrated that α-hydroxyketone (2) exists in a conformational equilibrium among 2a, 2b, and 2c. The 2a conformer predominantly exists in a polar medium and at low temperatures, whereas the 2bconformer is more stable than 2ain a nonpolar medium. On the other hand, the epimer (3) exists preferentially in the 3aconformation in both polar and nonpolar media and at low temperatures. The CD curves of compounds 6and 7exhibited the exactly same behavior as those in compounds (2) and (3) respectively. These results are interpreted in terms of the competition of the steric factor and the intramolecular hydrogen bonding.

Temperature-dependent circular dichroism measurements in the n−π*transition enabled us to predict the preferred rotational conformation of the acetyl and the formyl groups of such monoterpene α,β-unsaturated carbonyl compounds as (+)-1-acetyl-4-methylcyclohexene (1), (−)-perillaldehyde (2), (+)-1-acetyl-2,4-dimethyl-cyclohexene (3), and(−)-myrtenal (4).

(1) Oxidation of dl-a-terpineol with tert-butyl chromate yeilded 8-hydroxypiperitone, which has not previously been described, 8-hydroxycarvotanacetone and homoterpenyl methyl ketone. In this case the oxidative fission of the double bond in the ring took place to a remarkable extent.(2) Oxidation of dl-a-terpinyl acetate with tert-butyl chromate gave 8-acetoxypiperitone, 8-acetoxycarvotanacetone, (neither have previously been described) and homoterpenyl methyl ketone. In this oxidation the cleavage of the ethylenic linkage was suppressed, and the yield of 8-acetoxycarvotanacetone was relatively good.Moreover, the effects of the solvent, acetic acid, benzoyl peroxide, air and the reaction temperature, on the yield of 8-acetoxycarvotanacetone wre investigated.(3) 8-acetoxycarvotanacetone was converted into dl-carvone when acetic acid was eliminated by pyrolysis.(4) The synthesis of carvone from a-terpinyl acetate was attiained through the intermeidate of 8-acetoxycarvotanacetone The overall of carvone from a-terpinyl acetate was 28% mole%.

The intramolecular interaction of oxirane and cyclopropane rings with a hydroxyl group in the alicyclic α,β-epoxy-, β,γ-epoxy-, and cyclopropyl alcohols was investigated by means of the infrared spectroscopy. cis-α,β-Epoxyalcohols (II, IV and V) showed a free hydroxyl band, an interacted hydroxyl band with a C–O bond of the oxirane ring, and/or a band due to a O–H···O hydrogen bond, whereas trans-epoxyalcohols (I and III) showed only a free hydroxyl band. The interaction between the hydroxyl group and a C–C bond of the oxirane ring was likely to be absent. β,γ-Epoxyalcohols revealed a hydroxyl band interacting with lone-pair electrons of the oxirane oxygen, in addition to a free hydroxyl band. The O–H··· cyclopropane interaction was found with 2-(1-methylcyclopropyl)-5-methylcyclohexanols (VII and VIII). The correlation of the infrared spectra with the conformation of the interacting groups is also discussed.

The conformations of flexible, cyclic α,β-unsaturated ketones, (−)-p-menth-3-en-5-one (1), (+)-carvone (2), (−)-piperitone (3), (−)-carvenone (4), and (+)-pulegone (5), were examined by means of the temperature-dependent circular dichroism (CD) in the region of the n-π*transition. In polar solvents, the simultaneous occurrence of the conformational equilibrium and the asymmetric solvation was observed markedly for the compound 1of these compounds, along with a change in the large rotational strength at lower temperatures.

The conformational analysis of the acetyl group of a stereoisomeric pair of 4-methyl-10-nor-8-oxomenthols was made by means of the temperature-dependent circular dichroism. (1R:3S:4R)-(+)-4-Methyl-10-nor-8-oxoneomenthol (1) exhibited a double-humped Cotton effect at a low temperature. This phenomenon seems to indicate the existence of a conformational equilibrium among 1b, 1c, and 1d, but not 1a. On the other hand (1R:3R:4R)-(−)-4-methyl-10-nor-8-oxomenthol (3) exhibited an inversion in the sign of the Cotton effect when the solvent and the temperature were changed. This phenomenon was interpreted in terms of the conformational equilibrium among 3a, 3b, and 3c. These phenomena were interpreted in terms of the competition of the steric factor and the intramolecular hydrogen bonding.

The oxidation of (+)-3-carene with t-butyl chromate was found to afford 3,α-dimethylstyrene (2), eucarvone (3), 1,1,4-trimethylcyclohepta-2,4-dien-6-one (4), 3-methylacetophenone (5), 8-hydroxy-m-cymene (6), car-3-en-2-one (7), (−)-car-3-en-5-one (8), and (−)-car-3-ene-2,5-dione (9). The aromatized compound (6) was a major product in the oxidation in an acidic medium, whereas the oxidation in the neutral and the basic media gave the enedione (9) and the enone (8) as major products. It was, furthermore, proved that methylenes adjacent to the cyclopropane ring of (−)-cis-carane (10) and (+)-caran-3β-ol (11) were scarcely attacked by t-butyl chromate.

Geraniol and citronellol were biosynthesized from [2-14C]mevalonic acid by the leaves of Pelargonium roseum Bourbon, The degradation of the radioactive specimens revealed that the major radioactivity (70–80%) was located at C-4 in the skeleton derived presumably from isopentenyl pyrophosphate and the rest of the activity at C-8 (and/or C-10) in the moiety from 3,3-dimethylallyl pyrophosphate. The unbalance of labeling was distinct from the result observed for the monoterpenes biosynthesized from the same labeled precursor by the flowers of the rose. A discussion is given on factors causing such a discrepancy in the labeling pattern owing to the difference of the plant and/or the organ. Time-course experiments with the use of [2-14C]mevalonic acid indicated the formation of geraniol prior to citronellol both in the intact plant and in the cell-free extract.