synthetic and structural studies in terpenoids

Abstract

The thesis entitled “Synthetic and Structural Studies in Terpenoids” consists of three chapters.

Chapter I deals with synthetic studies on diterpenoids calyenone (1), calyone (2), and precalyone (3) isolated from Roylea calycina (Roxb.) Briq. The synthesis of 1,1,4a(3-trimethyl-2?-acetoxy-1,2,3,4,4a,8a?-hexahydronaphthalen-7(8H)-one (12), a key intermediate in the synthesis of calyenone (1), was accomplished by two independent routes.

In the first route, the acetoxy enone (12) was obtained in six steps from the known hydroxy ketone (6), prepared from 8a-methyl-3,4,8,8a-tetrahydronaphthalen-1(2H),6(6H)-dione (5).

Sodium borohydride reduction of ketone (6) gave the dihydroxy compound (7), which on treatment with acetic anhydride and pyridine gave the diacetate (8).

Allylic oxidation of (8) with potassium chromate in acetic acid and acetic anhydride gave the enone diacetate (9) in 65% yield.

Lithium–ammonia reduction of (9) gave the dihydroxy ketone (10), which underwent dehydration with potassium carbonate in methanol to give the hydroxy enone (11).

Acetylation of (11) with acetic anhydride and pyridine gave the acetoxy enone (12).

In an alternative route, acetoxy enone (12) was prepared by bromination and dehydrobromination of ketone (18), derived from unsaturated ketone (13). Woodward alkylation of (13) with potassium t-butoxide in t-butanol and methyl iodide gave trimethyl ketone (14). Reduction with sodium borohydride followed by acetylation gave acetate (15). Oxidation of (15) with potassium chromate yielded acetoxy enone (16). Stereoselective reduction of (16) with metal–ammonia solution gave hydroxy ketone (17) with trans AB ring junction, which was acetylated to give acetoxy ketone (18).

Homologation of 3-furoic acid by Arndt–Eistert synthesis gave 3-furanacetic acid (19). Reduction with lithium aluminium hydride afforded alcohol (20), converted into bromide (21) with phosphorus tribromide in pyridine. Coupling of fragments (11) and (21) was accomplished by copper-catalyzed 1,4-addition on enone (11) with furanethylmagnesium bromide, followed by in situ methylation with methyl iodide to give 3?-hydroxy-15,16-epoxylabda-13(16),14-dien-7-one (4).

Further transformation to calyenone could not be carried out due to paucity of material. Calyenone treated with lithium in liquid ammonia afforded a compound not identical with synthetic material (4), leading to revision of the structures and configuration of calyenone (1), calyone (2), and precalyone (3), with the acetoxyl group present as 3?-axial. PMR spectral data and NOE experiments supported the revised configuration.

Chapter II describes synthetic investigations on eremolactone (22), a diterpene isolated from Eremophila freelingii F. Muell. An attempted synthesis of trimethyl aldehyde (23), a key intermediate in the total synthesis of eremolactone, is discussed.

Birch reduction of 1-methyl-6-methoxyindane gave 1-methyl-6-methoxy-4,7-dihydroindane.

Reaction with chloroacrylonitrile in the presence of dichloromaleic anhydride gave adduct (24).

Hydrolysis with KOH–DMSO yielded tricyclic ketone (25).

Formylation with ethyl formate and sodium methoxide gave hydroxymethylene compound (26).

Treatment with isopropyl iodide and potassium carbonate afforded isopropoxymethylene ketone (27).

Grignard reaction with methylmagnesium iodide followed by acidic work-up did not yield the desired unsaturated aldehyde (28).

To understand the reaction outcomes, methylmagnesium iodide and methyllithium additions were studied on model systems (29, 30, 31) under varied conditions.

Chapter III deals with the isolation and structure elucidation of triterpenes from Barringtonia speciosa Forst.

Section I reviews the chemistry of Barringtonia species, emphasizing medicinal value and structure determination of acidic and neutral triterpenes.

Section II describes isolation and structure elucidation of two new triterpenedicarboxylic acids: anhydrobartogenic acid (32) and 19-epibartogenic acid (34), in addition to bartogenic acid (36) from the fruits of Barringtonia speciosa.

The structures were established as:

Anhydrobartogenic acid (32): 2?,3?-dihydroxyolean-12,18-dien-24,28-dioic acid

19-epibartogenic acid (34): 2?,3?,19?-trihydroxyolean-12-en-24,28-dioic acid