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An efficient synthesis of both enantiomers of lycoperdic acid, a 4-hydroxyglutamic acid derivative from edible mushroom Lycoperdon perlatum, was achieved from a chiral aminoalcohol. The key steps were a stereoselective introduction of a C3 unit into a bicyclic ketone and oxidative cleavage of a cyclic vicinal diol into a dicarboxylic acid. This report provides the first synthesis of (−)-lycoperdic acid.

The heterothallic group of the plant pathogen Phytophthora can sexually reproduce between the cross-compatible mating types A1 and A2. The mating hormone α2, produced by A2 mating type and utilized to promote the sexual reproduction of the partner A1 type, is known to be biosynthesized from phytol. In this study, we identified 2 biosynthetic intermediates, 11- and 16-hydroxyphytols (1 and 2), for α2 by administering the synthetic intermediates to an A2-type strain to produce α2 and by administering phytol to A2 strains to detect the intermediates in the mycelia. The results suggest that α2 is biosynthesized by possibly 2 cytochrome P450 oxygenases via 2 hydroxyphytol intermediates (1 and 2) in A2 hyphae and secreted outside.

An efficient synthetic pathway to acylpyrrolidinones via a nitro-Mannich reaction, followed by the intramolecular 1,3-dipolar cycloaddition of a nitrile oxide to an alkyne was developed. The syntheses of a leucine-derived tetramic acid and natural tetramide (+)-laccarin were achieved in five steps using aldehydes, 2-alkynamides and nitromethane as the carbon sources.

The first synthesis of (7S,9R)-decarestrictine H and (7R,9R)-decarestrictine H as well as the improved synthesis of decarestrictine J were achieved. The overall yields of (7S,9R)-decarestrictines H and J were 20.9% each in nine to ten steps from (R)-Roche ester using a unified synthetic route via esterification with 3,3-ethylenedioxyhex-5-enoic acid and ring-closing metathesis, which were the key steps. The relative stereochemistry of decarestrictine H was determined to be 7,9-syn by comparing the spectral data of the natural product and synthetic epimers of decarestrictines H.

Formosusin A, a specific inhibitor of an X-family DNA polymerase (rat DNA polymerase β), was synthesized using a Sharpless asymmetric dihydroxylation as the key step for the preparation of a chiral building block. This Letter describes the first example of the total synthesis of formosusin A. The absolute configuration of the natural formosusin A was determined to be ( R ) from the specific rotation value. Racemization of formosusin A was observed under acidic conditions, suggesting that the reported natural product might have low optical purity.

Cochlearol A, a renoprotective meroterpenoid isolated from Ganoderma cochlear, was formally synthesized by intramolecular acetal formation. Its characteristic perhydro-3,9a-epoxybenzo[c]oxepine skeleton was stereoselectively constructed by intramolecular acetal formation employing spiroepoxide as a key intermediate, which was prepared via benzylic oxidation under Nicolaou’s conditions employing photochemically activated Pb(OAc)4 and introduction of epoxide under Concellon’s conditions using diiodomethane and methyllithium.

The stereochemistry of selective anticancer compound FE399 was determined to be rel-9R,14R,17R by theoretical and synthetic studies. Relative stereochemistry of FE399 was predicted by comparison of the 13C NMR chemical shifts of the natural sample with that predicted by theoretical calculation for each possible stereoisomer. The first synthesis of (9R,14R,17R)-(−)-FE399 was achieved using an amide formation of a dithiazocane with a hydroxy dodecanoic acid derivatives and sixteen-membered macrolactonization as key steps. The overall yield was 18% in ten steps from l -cysteine and (S)-glycidyl tosylate.

Both enantiomers of (Z)-2β-hydroxy-14-hydro-β-santalol, a potent anti-H. pylori agent, were synthesized and the absolute configuration of the natural product was determined to be 1R,2S,3R,4S. The bicyclo[2.2.1]heptane skeleton was efficiently constructed employing tandem radical cyclization of tethered precursor. Both enantiomers were prepared via optical resolution of racemic intermediate.

The stereochemistry of decarestrictine G was revised to be 5R,6R,9R from theoretical and synthetic studies. The presumable stereoisomer was estimated by comparison of the 1H NMR chemical shifts of the natural product with the calculated values based on density functional theory. With this finding, a synthetic study was performed, and the spectroscopic data for the synthetic (5R,6R,9R)-isomer was fully identical to those of the natural product. The synthesis of (5R,6R,9R)-(−)-decarestrictine G was achieved in 16.5% overall yield in six steps from methyl 3-oxohex-5-enoate via a ring-closing metathesis and a face-selective dihydroxylation of a ten-membered lactone system as the key steps.

In response to environmental stressors such as blast fungal infections, rice produces phytoalexins, an antimicrobial diterpenoid compound. Together with momilactones, phytocassanes are among the major diterpenoid phytoalexins. The biosynthetic genes of diterpenoid phytoalexin are organized on the chromosome in functional gene clusters, comprising diterpene cyclase, dehydrogenase, and cytochrome P450 monooxygenase genes. Their functions have been studied extensively using in vitro enzyme assay systems. Specifically, P450 genes (CYP71Z6, Z7; CYP76M5, M6, M7, M8) on rice chromosome 2 have multifunctional activities associated with ent-copalyl diphosphate-related diterpene hydrocarbons, but the in planta contribution of these genes to diterpenoid phytoalexin production remains unknown. Here, we characterized cyp71z7 T-DNA mutant and CYP76M7/M8 RNAi lines to find that potential phytoalexin intermediates accumulated in these P450-suppressed rice plants. The results suggested that in planta, CYP71Z7 is responsible for C2-hydroxylation of phytocassanes and that CYP76M7/M8 is involved in C11α-hydroxylation of 3-hydroxy-cassadiene. Based on these results, we proposed potential routes of phytocassane biosynthesis in planta.

It is well known that there are nine stereoisomers of inositol that are composed of seven achiral compounds with a pair of enantiomers. However, there is no report regarding larger inositol homolog...

The first enantioselective syntheses of ganomycin I, a meroterpenoid isolated from the Vietnamese mushroom Ganoderma colossum, and the related meroterpenoid fornicin A were accomplished. Our methodology for the total syntheses of these compounds featured the construction of the butenolide moiety by asymmetric dihydroxylation followed by Julia–Kocienski type olefin formation and ring-closing metathesis reactions. The absolute configurations of the two natural products were determined by comparisons of specific rotation. A cell-based assay of the synthetic compounds with transfected human embryonic kidney 293 tet-off (E-PR293) cells indicated that ganomycin I possesses cytotoxicity and fornicin A possesses weak anti-HIV-1 protease activity without cytotoxicity.

The first total syntheses of 5′-O-desmethylterphenyllin and three related p-terphenyls have been achieved. The methodology features a Suzuki–Miyaura coupling reaction with a hindered aryl chloride as the key step. Two of the four synthesized 5′-O-desmethylterphenyllins exhibit moderate TNF-α release-inhibitory activity toward RBL-2H3 cells.

The first total synthesis of virgineone aglycone has been achieved employing the tandem O -acylation–migration reaction and the olefin cross-metathesis as key steps for fragment couplings. The left-hand segment of virgineone was also synthesized. The absolute configuration of the reported virgineone aglycone was determined to be (2 S ,7 RS ,26 S ) based on NMR analyses and the specific rotation values of the synthetic compounds. The absolute configuration of the natural virgineone was presumed to be (2 S ,7 S ,26 S ) based on NMR analyses of the synthetic virgineone aglycone.

Formosusin A, a specific inhibitor of an X-family DNA polymerase (rat DNA polymerase β), was synthesized using a Sharpless asymmetric dihydroxylation as the key step for the preparation of a chiral building block. This Letter describes the first example of the total synthesis of formosusin A. The absolute configuration of the natural formosusin A was determined to be ( R ) from the specific rotation value. Racemization of formosusin A was observed under acidic conditions, suggesting that the reported natural product might have low optical purity.

Four stereoisomers of Phytophthora mating hormone α2 were synthesized using both enantiomers of citronellol as starting materials. The absolute configuration of the natural product was determined to be 7 S ,11 R ,15 R by oospore-inducing assays of the synthetic isomers. A concise synthetic procedure of α1 was also established using a common synthetic intermediate of α2.

A proposed structure for the diffusible extracellular factor (DF) of Xanthomonas campestris pv. campestris (Xcc) has been synthesized. Its MS spectrum and biological activity, however, contradict those of the natural product previously reported, suggesting that the structure for DF of Xcc must be reexamined.

An asymmetric total synthesis of ent-sandaracopimaradiene, a biosynthetic intermediate of oryzalexins, via B-alkyl Suzuki-Miyaura coupling and Lewis acid-mediated B-ring formation as key steps was achieved.

A convergent synthetic strategy for abietane diterpenoids via B -alkyl Suzuki–Miyaura coupling and Lewis acid-mediated cyclization reactions is established. Asymmetric total synthesis of 12-deoxyroyleanone, an antileishmanial diterpene, is described.

Two stereoisomers of penazetidine A (1a), the azetidine alkaloid isolated from the Indo-Pacific marine sponge Penares sollasi, were synthesized by starting from (S)-serine and (R)-or (S)-citronellol. The natural penazetidine A must be either (2S,3R,4S,12′R)- or (2S,3R,4S,12′S)-1a.

The structure of the antibacterial sesquiterpene from Premna oligotricha was shown to be not 1 but 2 (relative stereochemistry) by the unambiguous synthesis of both (±)-1 and (±)-2.

The heterothallic species of the agricultural pest Phytophthora use mating hormones α1 and α2 to regulate their sexual reproduction. Here we describe the absolute stereostructure of the second mating hormone α2 as defined by spectroscopic analysis and total synthesis. We have uncovered not only the interspecies universality of α hormones but also the pathway by which α2 is biosynthesized from phytol by A2-mating type strains and metabolized to α1 by A1 strains.

Phytocassane A–E possess ent -cassane skeleton because synthetic (+)-2-deoxyphytocassane A with cassane skeleton showed the Cotton effects positive at 369 nm (due to the ring-C dienone chromophore) and negative at 289 nm (due to the ring-A carbonyl group), while the natural phytocassane A exhibited the opposite Cotton effects.

The first total synthesis of ent-cassa-12,15-diene, a putative precursor of diterpene phytoalexins, was accomplished.

The four stereoisomers of small bacteriocin, an autoinducer of the symbiotic nitrogen-fixing bacterium Rhizobium leguminosarum, were synthesized via a versatile methodology for 3′-hydroxyacyl homoserine lactones based on the Nagao asymmetric aldol reaction. The synthetic isomers were much less effective at inhibiting the growth of R. leguminosarum RBL5523 than the natural isomer, showing the importance of stereochemistry for activity.

Summary We have isolated and characterized a cDNA encoding a novel diterpene cyclase, OsDTC1, from suspension-cultured rice cells treated with a chitin elicitor. OsDTC1 functions as ent-cassa-12,15-diene synthase, which is considered to play a key role in the biosynthesis of (−)-phytocassanes recently isolated as rice diterpenoid phytoalexins. The expression of OsDTC1 mRNA was also confirmed in ultraviolet (UV)-irradiated rice leaves. In addition, we identified ent-cassa-12,15-diene, a putative diterpene hydrocarbon precursor of (−)-phytocassanes, as an endogenous compound in the chitin-elicited suspension-cultured rice cells and the UV-irradiated rice leaves. The OsDTC1 cDNA isolated here will be a useful tool to investigate the regulatory mechanisms of the biosyntheis of (−)-phytocassanes in rice.

A novel pyrrolidine amide (MQ-A3) isolated from the tropical convolvulaceous species was synthesized in 5 steps by starting from commercially available 12-bromododecanol and (S)-2-methylbutylbromide. The absolute configuration of the natural product was confirmed by a comparison of the specific rotation values.

The Ohrui-Akasaka method is the only one methodology to solve the intrinsic problem of diastereomer method. The Ohrui-Akasaka ester discriminates an asymmetric center remote from up to 24 carbons. The gauche effect combined with CH-π interaction of the ester sets anthracene ring close to acyl side chain. The distinctive conformation provides a chiral field to a remote asymmetric center. This review describes the examples of the determination of the absolute configuration of the natural products, leustroducsin B, S 365 A and plakoside A, by using the Ohrui-Akasaka method.