Kentaro Okano

Total Synthesis of Dictyodendrin A and B

alkaloids known to possess inhibitory activity against telomerase. As telomerase is expressed in most tumor cell lines and its activity is associated with cell proliferation, telomerase inhibition represents a potential target for cancer chemotherapy. These compounds have received considerable attention as synthetic targets, not only owing to their intriguing biological activity but also to their characteristic structure, having the highly substituted pyrrolo[2,3-c]carbazole core. Among numerous studies toward dictyodendrin synthesis, only F rstner and co-workers succeeded in the total synthesis of dictyodendrins B, C, and E, which was followed by the recent total synthesis of dictyodendrin B by Iwao and coworkers. Herein, we report the first total synthesis of dictyodendrin A (1) and a total synthesis of B (2) which features a hitherto unprecedented benzyne-mediated one-pot cyclization/cross-coupling sequence. In planning the synthesis of dictyodendrins, we designed a flexible route involving introduction of peripheral segments on the pivotal indoline intermediate 3 (Scheme 2). Thus, the

Total Synthesis of (−)‐Acetylaranotin

The key step in this total synthesis of (-)-acetylaranotin is the efficient formation of the characteristic dihydrooxepine ring from cyclohexenone through an unusual vinylogous Rubottom oxidation and a regioselective Baeyer-Villiger oxidation. (-)-Acetylaranotin is obtained in 22 steps from commercially available L-Cbz-tyrosine (Cbz=benzyloxycarbonyl).

Concise Total Synthesis of (−)-Mersicarpine

A concise total synthesis of (-)-mersicarpine from a known cyclohexanone was accomplished. The azepinoindole core was constructed by a DIBAL-H-mediated reductive ring-expansion reaction of oxime.

Total synthesis of dictyodendrins A-E.

A highly efficient total synthesis of dictyodendrins A-E was accomplished. The synthesis features a novel benzyne-mediated one-pot indoline formation/cross-coupling sequence for the construction of a highly substituted key indoline intermediate. Peripheral substituents were introduced onto this intermediate in a modular fashion to complete the total synthesis of dictyodendrins A-E.

Synthesis of Substituted Indoline and Carbazole by Benzyne-Mediated Cyclization–Functionalization

A benzyne-mediated synthesis of substituted indolines and carbazoles was developed. The reaction includes generation of benzyne using Mg(TMP)2·2LiCl as a base, cyclization, and trapping the resulting organomagnesium intermediate with an electrophile to provide a series of substituted indolines and carbazoles in a regiospecific manner. This was applied to a concise five-pot total synthesis of heptaphylline.

Total synthesis of PDE-II by copper-mediated double amination

A concise total synthesis of PDE-II featuring copper-mediated double aryl amination with the combination of CuI, CsOAc, and Cs2CO3 is described. The highly substituted pyrroloindole skeleton was constructed by a one-pot five-step sequence including double aryl amination, beta-elimination, deprotection of a Cbz group, and removal of an Ns group followed by rearomatization.

Enantioselective total synthesis of (-)- and (+)-petrosin.

The enantioselective total synthesis of (-)- and (+)-petrosin is described. The union of two key segments was executed by Suzuki-Miyaura coupling. The quinolizidine rings were stereoselectively constructed via a diastereoselective Mannich reaction and an aza-Michael reaction. The 16-membered ring was constructed by ring-closing metathesis with the second-generation Grubbs catalyst.

Total Synthesis of (−)‐Histrionicotoxin through a Stereoselective Radical Translocation–Cyclization Reaction

Stereoselective total syntheses of (-)-histrionicotoxin and (-)-histrionicotoxin 235A are described. The 1-azaspiro[5.5]undecane skeleton was constructed diastereoselectively by a radical translocation-cyclization reaction involving a chiral cyclic acetal; the use of tris(trimethylsilyl)silane was crucial for the high diastereoselectivity. The cyclization product was converted into (-)-histrionicotoxin 235A through a one-pot partial-reduction-allylation reaction of a derivative containing an unprotected lactam. Finally, two terminal alkenes were transformed into enynes with the 1,3-amino alcohol protected as an oxathiazolidine oxide to complete the total synthesis of (-)-histrionicotoxin.

Total Synthesis of (+)‐MPC1001B

The first total synthesis of an epidithiodiketopiperazine alkaloid, (+)-MPC1001B, was accomplished. This synthesis features a tetra-n-butylammonium fluoride mediated intramolecular aldol reaction for forming the 15-membered macrolactone ring, and the construction of an epidithiodiketopiperazine substructure through a stepwise sulfenylation reaction involving a novel trityl trisulfide (TrSSS)-group transfer.

Ring-Expansion Reaction of Oximes with Aluminum Reductants

The ring-expansion reactions of heterocyclic ketoximes and carbocyclic ketoximes with several reductants such as AlHCl2, AlH3 (alane), LiAlH4, LiAlH(OtBu)3, and (MeOCH2CH2O)2AlH2Na (Red-Al) were examined. Among reductants, AlHCl2 (LiAlH4:AlCl3 = 1:3) in cyclopentyl methyl ether (CPME) has been found to be a suitable reagent for the reaction, and the rearranged cyclic secondary amines were obtained in good to excellent yields.