A pharmaceutically important natural product, β-lapachone, was efficiently synthesized in four steps in 70 % overall yield starting from commercially available 1,4-naphthoquinone. The key step of the synthesis was the direct conversion of 2-prenyl-1,4-naphthoquinone into β-lapachone through an advantageous cyclization/hydration/oxidation cascade process.

A biologically attractive and structurally unique marine natural product, (+)-liphagal, was biomimetically synthesized in 29 % overall yield in a longest linear sequence of 13 steps from commercially available (+)-sclareolide. This synthesis involved the following crucial steps: (i) stereocontrolled hydrogenation of an endo-olefinic decalin to install the C8 stereogenic centre present in the requisite decalin segment; (ii) coupling of the decalin segment with an aromatic moiety to assemble the desired carbon skeleton; (iii) ring expansion of a proposed biogenetic intermediate followed by benzofuran formation to establish the requisite tetracyclic core structure. A few new aspects of the proposed biosynthetic pathway to this class of natural products were revealed.

Dysidavarone A, a structurally unprecedented sesquiterpenoid quinone, was synthesized in 30 % overall yield in a longest liner sequence of 13 steps from commercially available o-vanillin. A highly strained and bridged eight-membered carbocyclic core was established by the C7C21 carbon bond formation through a copper enolate mediated Michael addition to the internal quinone ring.

A biologically attractive and structurally unique marine natural product, (+)-strongylin A (1), was synthesized for the first time by starting from a known trans-decalone derivative (19 % overall yield in 11 steps). The synthetic method involved the following key steps: (i) stereocontrolled hydrogenation of an exo-olefinic decalin to install the C8 stereogenic centre present in the required decalin segment; (ii) coupling of the decalin segment with an aromatic moiety to assemble the desired carbon skeleton; and (iii) sequential BF₃·Et₂O-induced dehydroxylation/rearrangement/cyclization of a decalin tertiary alcohol to directly produce target compound 1. This total synthesis has established the absolute configuration of the natural product.

Bauhinoxepin J possessing antimycobacterial, antimalarial, and tumor growth inhibitory activities was efficiently synthesized. The method involves crucial steps, including a coupling reaction of two aromatic moieties to construct the desired carbon framework, chemoselective phenol oxidation of a bisphenol derivative to establish a key cyclization precursor, and construction of a characteristic seven-membered dihydrooxepin ring by internal cyclization to yield the target bauhinoxepin J.

Potential immunosuppressive diterpenoid pyrones (–)-subglutinols A and B were efficiently synthesized in an enantioselective manner starting from a known trans-decalone derivative. The synthetic method involved the following key steps: (i) [2,3]-Wittig rearrangement of a stannyl methyl ether to access the requisite decalin segment; (ii) coupling of the decalin segment with a γ-pyrone moiety to set up the desired carbon framework; (iii) construction of a characteristic tetrahydrofuran ring in one-pot fashion through an internal S_N2-type cyclization, and (iv) conversion of a γ-pyrone moiety into an α-pyrone ring to yield the target (–)-subglutinols A and B.

A novel and potent hemagglutinin inhibitor, (+)-stachyflin, was efficiently synthesized in an enantioselective manner starting from the (+)-5-methyl-Wieland–Miescher ketone. The synthetic method features a BF₃·Et₂O-induced cascade epoxide-opening/rearrangement/cyclization reaction tostereoselectively construct the requisite pentacyclic ring system in one step. In order to rationalize the mechanism of the cascade reaction, quantum chemical calculations of the possible intermediary carbocations and transition states in the model synthesis were carried out. An alternative approach to synthesize (+)-stachyflin by employing a similar cascade reaction was also described.

The bicyclic depsipeptide histone deacetylase (HDAC) inhibitors spiruchostatins A and B, 5′′-epi-spiruchostatin B and FK228 were efficiently synthesized in a convergent and unified manner. The synthetic method involved the following crucial steps: i) a Julia–Kocienski olefination of a 1,3-propanediol-derived sulfone and a L- or D-malic acid-derived aldehyde to access the most synthetically challenging unit, (3S or 3R,4E)-3-hydroxy-7-mercaptohept-4-enoic acid, present in a D-alanine- or D-valine-containing segment; ii) a condensation of a D-valine-D-cysteine- or D-allo-isoleucine-D-cysteine-containing segment with a D-alanine- or D-valine-containing segment to directly assemble the corresponding seco-acids; and iii) a macrocyclization of a seco-acid using the Shiina method or the Mitsunobu method to construct the requisite 15- or 16-membered macrolactone. The present synthesis has established the C5′′ stereochemistry of spiruchostatin B. In addition, HDAC inhibitory assay and the cell-growth inhibition analysis of the synthesized depsipeptides determined the order of their potency and revealed some novel aspects of structure–activity relationships. It was also found that unnatural 5′′-epi-spiruchostatin B shows extremely high selectivity (ca. 1600-fold) for class I HDAC1 (IC₅₀=2.4 nM) over class II HDAC6 (IC₅₀=3900 nM) with potent cell-growth-inhibitory activity at nanomolar levels of IC₅₀ values.

Biologically important and structurally unique marine natural products avarone (1), avarol (2), neoavarone (3), neoavarol (4) and aureol (5), were efficiently synthesized in a unified manner starting from (+)-5-methyl-Wieland–Miescher ketone 10. The synthesis involved the following crucial steps: i) Sequential BF₃⋅Et₂O-induced rearrangement/cyclization reaction of 2 and 4 to produce 5 with complete stereoselectivity in high yield (2 5 and 4 5); ii) strategic salcomine oxidation of the phenolic compounds 6 and 8 to derive the corresponding quinones 1 and 3 (6 1 and 8 3); and iii) Birch reductive alkylation of 10 with bromide 11 to construct the requisite carbon framework 12 (10 + 11 12). An in vitro cytotoxicity assay of compounds 1–5 against human histiocytic lymphoma cells U937 determined the order of cytotoxic potency (3 > 1 > 5 > 2 > 4) and some novel aspects of structure-activity relationships.