Semisynthetic Studies Establish a Role for Conjugate Halide Exchange in the Formation of Chlorinated Pyrroloiminoquinones and Related Alkaloids.

Two novel pyrroloiminoquinone alkaloids, 6-chlorodamirone A and 6-bromodamirone A, have been identified for the first time from the marine sponge sp. (order: Poecilosclerida: family Latrunculiidae), sourced from Western Australia. Alongside these new compounds, seven previously known metabolites were also isolated.

Antibody-mimetic drug conjugate with efficient internalization activity using anti-HER2 VHH and duocarmycin.

Antibody-mimetic drug conjugate (AMDC) is a cancer cell-targeted drug delivery system based on the non-covalent binding of mutated streptavidin and modified biotin, namely Cupid and Psyche. However, the development of AMDCs is hampered by difficulties in post-translational modification or poor internalization activity. Here, we report an expression, refolding, and purification method for AMDC using a variable heavy chain of heavy chain-only antibodies (VHHs).

Unified Divergent Total Synthesis of Discorhabdin B, H, K, and Aleutianamine via the Late-Stage Oxidative -Acetal Formation.

This study achieved the total syntheses of (+)-discorhabdin B, (-)-discorhabdin H, (+)-discorhabdin K, and (-)-aleutianamine. A phenethylamine fragment bearing a -pivaloylthio group, corresponding to the D/E/G ring moiety, was prepared from benzothiophen-2-carboxylic acid methyl ester and condensed with a known pyrroloiminoquinone derivative. The adduct was subjected to [bis(trifluoroacetoxy)iodo]benzene (PIFA)-promoted oxidative spirocyclization to furnish the A/B/C/D/E spirocyclohexadienone fused with pyrroloiminoquinone.

[Synthetic Studies on Complex Natural Products Based on Development of a Novel Synthetic Method for Heteroaromatic Skeleton].

Among my recent work on the syntheses of complex natural products based on the development of a novel synthetic method for the heteroaromatic skeleton, this article primarily deals with the total syntheses of (+)-CC-1065, isobatzeline A/B, and batzeline A. These syntheses were accomplished via a novel indole synthesis utilizing a ring expansion reaction of benzocyclobutenone oxime sulfonate as the key step. The 1,2-dihydro-3H-pyrrolo[3,2-e]indole segments of (+)-CC-1065 were rapidly constructed via a two-directional double-ring expansion strategy.

Cyclic Sulfamidite as Simultaneous Protecting Group for Amino Alcohols: Development of a Mild Deprotection Protocol Using Thiophenol.

This study describes the novel utility of cyclic sulfamidite as a simultaneous protecting group for 1,2- or 1,3-amino alcohols. An exceptionally mild and neutral condition for the removal of the cyclic sulfamidite was developed. The deprotection condition demonstrated a broad range of functional-group compatibility, including a substrate bearing a Z-enyne structure without any loss of double-bond stereochemistry.

Divergent Total Syntheses of Isobatzellines A/B and Batzelline A.

Divergent total syntheses of isobatzellines A/B and batzelline A were accomplished. A fully substituted common indole intermediate bearing C-2 methylthio and C-5 chloro groups was constructed via ring expansion of benzocyclobutenone oxime sulfonate with NaSMe and a benzyne-mediated cyclization/functionalization sequence as the key steps. The total synthesis of isobatzelline B was achieved via formation of the iminoquinone structure by the redox-neutral acid-promoted C-5 proto-dechlorination of the common indole intermediate.

Total Synthesis of (-)-Lepadiformine A via Radical Translocation-Cyclization Reaction.

Total synthesis of (-)-lepadiformine A featuring construction of the 1-azaspiro[4.5]decane skeleton by a highly diastereoselective radical translocation-cyclization reaction of a γ-lactam derivative bearing a chiral butenolide moiety is described. The enantioselective construction of butenolide is conducted via Krische's catalytic asymmetric allylation protocol.

Total Synthesis of (+)-CC-1065 Utilizing Ring Expansion Reaction of Benzocyclobutenone Oxime Sulfonate.

An indole synthesis via ring expansion of benzocyclobutenone oxime sulfonate was developed. Utility of the indole synthesis was demonstrated by the total synthesis of (+)-CC-1065. The middle and right segments were constructed by a sequential ring expansion of the symmetrical benzo-bis-cyclobutenone.

Structural Determination of (-)-SCH 64874 and Hirsutellomycin by Semisynthesis.

The structure of a C-symmetric epidithiodiketopiperazine alkaloid, SCH 64874, was determined by semisynthesis. The relative stereochemistry of the β-hydroxy carboxylic acid chain having three chiral centers was determined by comparison of the NMR data of the four possible diastereomeric β-hydroxy carboxylic acid fragments with those of SCH 64874. Condensation of the (-)-deacetylaranotin core with two enantiomeric β-hydroxy carboxylic acids revealed the relative stereochemistry of SCH 64874.

Synthetic Study on Naphthospironone A: Construction of Benzobicyclo[3.2.1]octene Skeleton with Oxaspirocycle.

In connection with the total synthesis of naphthospironone A, a model study has revealed a promising approach to construct a benzobicyclo[3.2.1]octene skeleton possessing an oxaspirocycle by employing an intramolecular aldol cyclization.