14,15,17-Trinorlabdan-8,13-dione 6 was efficiently synthesized via ozonolysis of(+)-manool (4) followed by treatment with aqueous NaOH in the presence of tetra-n-butylammonium bromide as catalyst. This protocol has the advantages of high yield, mild conditions and simple procedure. Utilizing this strategy, the first enantiospecific synthesis of 13,14-dihydroxy-8,11,13-podocarpatrien-7-one (1), a constituent of Taiwania cryptomerioides and Celastrus paniculatus, was achieved starting from (+)-manool (4) after a four-step sequence in 24% overall yield.

13,14-Dihydroxy-8,11,13-podocarpatrien-7-one (1) and a series of ring C aromatic diterpene derivatives were synthesised from (+)-manool (4) and evaluated for their cytotoxic, leishmanicidal and trypanocidal activities. Our results indicated that compound 1 and other podocarpane-type intermediates are cytotoxic. Cleavage of C6-C7 bond of compound 7 improved cytotoxic activity, indicating that, in particular, the 6,7-seco-podocarpane-type compound 20 might serve as a lead compound for further development.

Twelve 13-benzyl-15,16-bisnorlabdanes in which the C-13 and C-14 substituents are varied have been prepared from the naturally occurring labdane diterpene (+)-manool. These synthesised compounds were evaluated for antimalarial activity, in vitro as hemozoin formation inhibitors and in vivo against Plasmodium berghei. These derivatives were also assayed for antileishmanial activity against Leishmania mexicana.

Abstractstarting from (+)‐manool (I)

Abstract A convenient synthesis of the natural (+)-13-hydroxypodocarpa-8,11,13-triene 1 and (+)-7-deoxynimbidiol 2 from (+)-manool 4 has been achieved in good overall yield.

Abstractvia β‐enone (III) as key intermediate

A practical method for the synthesis of naturally occurring ring C aromatic diterpenes from (+)-manool via key intermediate β-enone is described. The natural (+)-13-hydroxypodocarpa-8,11,13-triene, the antitumour (+)-7-deoxynimbidiol, and (+)-nimbidiol were prepared in good overall yields.

An efficient method for the synthesis of optically active labdane-type diterpenes from (+)-manool 8 is described. We prepared the natural labdane-type diterpene 5 via key intermediate peroxide 9, and synthetic hydroxybutenolides 6 and 7 via a furan photosensitised oxygenation reaction of labdafuran (14). Compounds 5, 6, 7 and 9 were evaluated as inhibitors of the β-haematin formation and globin proteolysis, and then were assayed in a malarial murine model. Compound 9 was the most promising compound, showing a positive correlation between in vitro and in vivo activities.

A practical method for the synthesis of optically active labdane-type diterpenes from (+)-manool 8, is described. We prepared the natural labdane-type diterpene 5 via key intermediate peroxide 9 and coronarin C 1, compound 8 and zerumin B 6 via a furan photosensitised oxygenation reactions.

A facile access to optically active (+)- ent -chromazonarol ent -1, isolated from the sponge Disidea pallescens , is reported from commercially available (+)-manool 4.

An efficient method for the synthesis of (+)-cyclozonarone 5, isozonarol Delta(8,9) 6 and isozonarone Delta(8,9) 7 via-the diene 4, obtained in two steps from manool 3, is described.

An efficient method for the synthesis of (+)-coronarin E 1, (+)- epi-coronarin A 2 and (+)-15, 16-epoxy-8(17), 13(16), 14-labdatriene 3 via the homodrimane 9, obtained in four steps from (+)-manool 5, is described.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An efficient method for the synthesis of (+)-cyclozonarone 5, isozonarol Δ8,9 6 and isozonarone Δ8,9 7 via the diene 4, obtained in two steps from manool 3, is described.

An efficient method for the synthesis of (+)-coronarin E (1), (+)-15,16-epoxy-8(17),13(16),14-labdatriene (2), and (+)-labda-8(17),13(Z)-diene-15,16-diol (3) from (+)-manool is described.

A facile synthesis of the sesquiterpene hydroquinone (+)-zonarol 5 and sesquiterpene quinone (+)-zonarone 6 from manool is reported in 7 and 8 steps, respectively.

One hundred and seventy four human subjects were studied to find out the interaction of vitamin A or beta-carotene with the inhibitors of iron absorption, from a basal breakfast containing bread from either 100 g of precooked corn flour or 100 g of white wheat flour, 50 g of cheese and 10 g of margarine. Bread was labeled with either 55Fe or 59Fe. This bread was made from commercially flours fortified with iron as ferrous fumarate and vitamins. It was noticed that the percentage of iron absorption from the breakfast prepared with precooked corn flour given alone and with different concentrations of coffee was practically the same, while the iron absorption from the breakfast prepared from wheat flour decreased from 6% when the breakfast was given alone, to less than 2% when it was given with different concentrations of coffee. The only ingredient present in precooked corn flour and not in wheat flour was vitamin A. This difference encouraged the authors to perform further experiments using precooked corn and wheat flours fortified only with ferrous fumarate. These studies demonstrated that vitamin A inhibits the effect of the polyphenol and partially inhibits the effect phytate on iron absorption. HPLC and spectrophotometric studies demonstrated an interaction between vitamin A and iron. Other experiments, which included 100 volunteers, were performed to test the effect of vitamin A and beta-carotene on iron absorption from corn, wheat and rice. The presence of vitamin A increased iron absorption up to 3 times for rice, 2.4 times for wheat and 1.8 times for corn. beta-carotene increased absorption almost 3 times for the three cereals tested, showing that both compounds were capable of preventing the inhibitory effect of phytates on iron absorption. This information suggest that vitamin A and beta-carotene form a complex with iron keeping it soluble in the intestinal lumen and preventing the inhibitory effect of phytates and polyphenols on iron absorption.