Synthesis of the C8-C20 and C21-C30 segments of pectenotoxin 2

In this study, we synthesized the C8-C20 and C21-C30 segments of the diarrhetic shellfish toxin pectenotoxin 2. The C8-C20 segment was assembled from a phosphonate corresponding to the C8-C15 segment (prepared from l-malic acid in 19 steps) and an aldehyde corresponding to the C16-C20 segment (synthesized from 3-methyl-3-butenol in nine steps) by a twelve-step process including the Horner-Wadsworth-Emmons reaction, regio- and stereoselective reduction of the resulting enone, diastereoselective epoxidation, and 5-exo epoxide cleavage forming the C-ring. The C21-C30 segment was constructed in 13 steps from (S)-glycidol via a route involving E-ring formation by 5-exo epoxide cleavage and stereoselective methylation at C27 by the Evans method.     

Improved synthesis of C8-C20 segment of pectenotoxin-2

The C8-C20 segment of pectenotoxin-2 was efficiently synthesized in 16% overall yield in 22 steps from l-malic acid via an improved route.     

Synthesis of the DE-ring of goniodomin A and prediction of its natural relative stereochemistry

Goniodomin A (1) was first isolated from Alexandrium hiranoi as a stereochemically unidentified antifungal agent in 1987 by Murakami. In this study, two stereoisomeric series of non-macrocyclic and macrocyclic DE-ring model compounds of 1 were synthesized, and the natural relative stereochemistry of the DE-ring was predicted by NMR comparison of 1 with these model compounds.     

Synthesis of the common FGHI-ring part of ciguatoxins

The common FGHI-ring part (2) of ciguatoxins has been synthesized from the F- and I-ring parts (6 and 5, respectively). The Nozaki-Hiyama-Kishi coupling of 6 with 5 followed by regio- and stereoselective epoxidation at C29 and C30 afforded an epoxide (4), which was transformed into a tricyclic compound (3) corresponding to the F-HI-ring part by 6-exo-epoxide opening and the subsequent inversion of the C29 stereocenter. Reductive cyclization of 3 forming the C31-O26 bond of the G-ring successfully produced 2.     

Synthesis of the C42-C52 part of ciguatoxin CTX3C

The C42-C52 part of ciguatoxin CTX3C (1) was synthesized from tri-O-acetyl d-glucal. The synthetic segment had a tetrahydropyran ring corresponding to the ‘C49-reduced’ L-ring of 1, designed to avoid side reactions due to acid-labile C49 acetal carbon during acidic reductive conditions planned in further synthesis toward 1. The vicinal dimethyl part at C47-C48 was constructed by a stepwise conjugate addition/methylation procedure. The C50-C52 unit was installed by Grignard addition of the C₃ unit followed by spirocyclization and reductive cleavage of the spirocyclic acetal. Stereoselective assembly of the C42-C44 part was achieved by Brown’s asymmetric crotylboration.     

Synthesis of the cyclohexene segment of portimine

The synthesis of the cyclohexene segment of portimine, a marine cytotoxin from the dinoflagellate Vulcanodinium rugosum, was achieved. The route includes an acylation/aldol reaction from 3-ethoxycyclohex-2-enone to create the C3 center, the 1,4-addition of a vinyl group at C16, the diastereoselective dihydroxylation of the vinyl group to generate the C15 center, a vinylation/dehydration sequence to set up the diene moiety, and stepwise installation of the amino-group-substituted C1 unit.     

Convergent synthesis of the ABCDE-ring part of ciguatoxin CTX3C

Convergent synthesis of the ABCDE-ring part (2) of ciguatoxin CTX3C (1) has been achieved. A carbanion stabilized by a dimethyldithioacetal S-oxide group in the AB-ring part (4) readily reacted with an aldehyde group in the E-ring part (5). The resulting adduct was facilely converted to the corresponding β,γ-unsaturated α,ε-dihydroxy ketone (3). The subsequent reductive hydroxy-ketone-cyclization reactions constructed the CD-ring part efficiently. Thus, the ABCDE-ring part (2) was concisely synthesized in 10 steps in 11% overall yield from the AB-ring and the E-ring parts (4 and 5).     

Convergent synthesis of the IJKLM-ring part of ciguatoxin CTX3C

Convergent synthesis of the IJKLM-ring part (2) of ciguatoxin CTX3C has been achieved from the I-ring and the L-ring parts (4 and 5) in total eight steps in 27% overall yield. The carbanion derived from 4, stabilized by a dimethyldithioacetal S-oxide group, was readily reacted with aldehyde 5 to give an adduct, which was facilely transformed into the corresponding α,ε-dihydroxy ketone 3. The JK-ring formation from 3 under reductive conditions followed by oxidative M-ring cyclization efficiently led to the pentacyclic ether 2. Improved synthesis of 6, a synthetic intermediate for 4, was also established.     

Formal total synthesis of hemibrevetoxin B by a convergent strategy

Concise construction of the trans-fused 7/7/6/6 tetracyclic ether part of hemibrevetoxin B (1) was achieved by a convergent strategy based on coupling reaction of an acyl anion equivalent, reductive cyclization of an α,ε-dihydroxyketone, and introduction of a methyl group at the central ring junction by the Nicolaou method. The resultant tetracyclic ether was transformed into the known intermediate, which was already converted to 1 by the Yamamoto group, thereby completing the formal total synthesis of 1.     

Highly Efficient,Convergent, and Enantioselective Synthesis of Phthioceranic Acid

A new strategy for highly concise, convergent, and enantioselective access to polydeoxypropionates has been developed. ZACA‐Pd‐catalyzed vinylation was used to prepare smaller deoxypropionate fragments, and then two key sequential Cu‐catalyzed stereocontrolled sp³–sp³ cross‐coupling reactions allowed convergent assembly of smaller building blocks to build‐up long polydeoxypropionate chains with excellent stereoselectivity. We employed this strategy for the synthesis of phthioceranic acid, a key constituent of the cell‐wall lipid of Mycobacterium tuberculosis, in just 8 longest linear steps with full stereocontrol.     

Synthesis and study of the antimalarial cardamom peroxide

A full account of our previously disclosed synthesis of the monoterpene dimer cardamom peroxide is reported. Inspired by hypotheses regarding the potential biosynthetic origins of this natural product, several unproductive routes are also reported. The chemical reactivity of this structurally unique metabolite in the presence of iron (II) sources is also reported as is its antimalarial activity against Plasmodium falciparum clinical isolates from several Cambodian provinces.     

Synthesis of the C21-C28 segment of pectenotoxin-4

The synthesis of the C21-C28 segment of pectenotoxin-4 as the C21 Weinreb amide is described. Feasibility studies for the union of a related Weinreb amide and a functionalized alkyne are also reported.     

天然产物goodyeroside A的全合成研究

以5-(S)-(d-盖氧基)-2(5H)-呋喃酮为起始原料．对具有肝保护活性的天然产物goodyeroside A进行了全合成研究。将合成所得目标产物的比旋光值及光谱数据与天然产物的数值相比较，两者一致，证明两者的结构与构型相同。     

Synthesis of the tetracyclic core of chlorospermines

Chlorospermines A and B are biologically interesting acridone natural products and recently isolated from Glycosmis chlorosperma.We report here a convergent approach to construct the tetracyclic core of the natural products.The two fragments are assembled together through Sonogashira coupling,and a cis-triene intermediate was prepared by using hydrosilylation/desilylation.A 6p-electrocyclization/aromatization sequence served as the key step of the synthesis,which formed the tetrasubstituted arene motif in one pot.     

Convergent synthesis of the common FGHI-ring part of ciguatoxins

Convergent synthesis of the common FGHI-ring part (54) of ciguatoxins was achieved via the following key steps: (i) the Nozaki-Hiyama-Kishi reaction connecting the F-ring part (6) with the I-ring part (7); (ii) regio- and stereoselective epoxidation; (iii) the 6-exo-epoxide opening reaction forming simultaneously the H-ring and the quaternary asymmetric center at C30; (iv) inversion of the C29 stereocenter by a two-step oxidation/reduction process, where the successful inversion depended on proper management of the steric environment of the substrate; and (v) final reductive cyclization constructing the G-ring.     

Synthetic approaches to the daphnane and tigliane diterpenes from aromatic precursors

Synthetic studies toward the daphnane and tigliane diterpenes, a large family of natural products from the plant families Euphorbiaceae and Thymelaeaceae, are reported. Retrosynthetic analysis traced these molecules back to an aromatic precursor and several routes were explored in the forward direction to access such motifs. Two strategies ultimately proved capable of forging complex 5,7,6-fused tricyclic ring systems, one of which proceeded in only seven steps.     

Synthesis of the cycloheptannelated indole fragment of dragmacidin E

Synthesis of the pivotal cycloheptannelated indole fragment of indole alkaloid dragmacidin E is achieved. The synthesis features a Pd-catalyzed indole synthesis reaction for the preparation of 3,7-disubstituted indole, a regioselective intramolecular Friedel–Crafts reaction for the construction of the 3,4-bridged cycloheptannelated indole skeleton, and a coupling reaction of vinyl triflate with diorganocuprate.