ChemInform Abstract: Acid‐Induced Favorskii‐Type Reaction: Regiocontrolled Elimination of Acyloin Mesylates Leading to α,β‐Unsaturated Ketones and Application to Formal Total Synthesis of (R)‐Muscone (XI) from Racemic Muscone.

The first part of this work details the formal total synthesis of HKI 0231B and the first total synthesis of both demethyl HKI 0231A and demethyl HKI 0231B. The formal synthesis used TBAF as a mild reagent to construct the indole. The total synthesis featured an efficient radical cyclization / oxidation step to construct the skeleton and a DDQ-mediated methoxylation reaction. The second part of this work is dedicated to the synthetic efforts towards the abeoergolines and the total synthesis of the abeo-ergoline analogs. In the synthetic study toward the abeo-ergolines, a reaction between 4-lithioindole and the enaminone, which was prepared from the ketone and Brederick reagent, effectively brought together all the necessary carbons for the final product. The synthesis of the abeo-ergoline analogs was direct, as it had a 36% overall yield in 7 steps. This approach is also flexible enough to allow the synthesis of various structurally related abeo-ergoline analogs. The third part of this work describes the invention of a new strategy which allows the one-pot benzocyclobutenol synthesis and the corresponding three-component reactions. In the reaction, acetaldehyde enolate and benzyne intermediates were generated in the same flask to produce benzocyclobutenoxides species which is in equilibrium with oqunodimethide species. With protonation, benzocyclobutenols were prepared in a one-pot fashion. With the addition of dienophiles, three component reactions were achieved. This strategy was also successfully applied in the synthesis of the berbine natural products when cyclic imines were used as dienophiles.

A formal synthesis of roseophilin, a novel pentacyclic structure possessing significant antitumor activity, starting from 3-cycloundecenylcarboxylic acid has been completed. The acid was converted diastereoselectively to the corresponding menthol ester via the ketene which, in turn, provided (S)-3-cycloundecenylcarboxaldehyde. Diastereoselective propargylation with propargyltriphenylstannane promoted by an asymmetric boron reagent prepared in situ from boron tribromide and the bis-p-toluenesulfonamide of (S,S)-stilbenediamine gave (1S,1‘R)-1-cycloundec-2‘-enylbut-3-yn-1-ol which set the stage for the key metathesis reaction. Platinum-catalyzed enyne metathesis via a formal [2 + 2] cycloaddition to a cyclobutene followed by conrotatory ring opening created the corresponding bicyclo[10.2.1]pentadeca-1(15),2-diene. Regioselective epoxidation of the less reactive double bond of the 1,3-diene was accomplished by 1,4-bromohydrin formation followed by base. Cuprate opening regio- and stereospecifically installed the isopropyl substituent. Standard procedures converted this intermediate to (1R,12R,13R,15R)-13-(tert-butyldimethylsiloxy)-15-isopropylbicyclo[10.2.1]pentadecane-3,14-dione. This diketone was converted to the corresponding unstable pyrrole by condensation with ammonium acetate, and the pyrrole nitrogen immediately alkylated with SEM-chloride. The formal synthesis was completed by conversion of the siloxy group to the corresponding ketone which previously had been condensed with the heterocyclic side chain to complete a synthesis of roseophilin. By having access to the tricyclic core asymmetrically for the first time, this route provides the opportunity to establish the absolute configuration of the natural product.

A formal total synthesis of the antitumor marine natural product (rac)‐renieramycin T, which possesses a characteristic ecteinascidin‐type A ring in the renieramycin–saframycin core skeleton, was elaborated. The key steps in the synthesis of (rac)‐renieramycin T are a modified Pictet–Spengler cyclization of dialkylated oxomalonate derivatives and decarboxylation via a monocarboxylic acid derivative followed by stereocontrolled protonation of the enol intermediate. A key intermediate in our previous synthesis of renieramycin T was used, and the formal synthesis was accomplished in 21 steps from a known piperazine‐2,5‐dione derivative.

A formal total synthesis of the potent anticancer agent Et-743 is described. The tetrahydroisoquinoline core is stereoselectively constructed using a novel radical cyclization of a glyoxalimine. Further elaboration of this core rapidly accessed the pentacyclic core of Et-743, but a mixture of regiosisomers was obtained in the key Pictet-Spengler ring closure. A known advanced intermediate in the synthesis of Et-743 was intercepted, constituting a formal synthesis of the molecule.

The formal total synthesis of the (+)-salicylihalamides A and B is detailed, utilizing a chiral pool approach to generate the three stereogenic centers and a ring-closing metathesis (RCM) for the formation of the macrocyclic ring structure. Starting from a known glucose-derived alcohol, the formal total synthesis was achieved in an efficient 13-step protocol in 26% overall yield. It was found that substitution at the remote phenolic group significantly influenced the ratio of the E- and Z-double bond products in the RCM step. The introduction of phenol protecting groups provided E-isomers preferentially and also enhanced the rates of the RCM reactions.

Enantioselective total and formal syntheses of paroxetine (PAXIL) via phosphine-catalyzed enone α-arylation using arylbismuth(V) reagents: a regiochemical complement to Heck arylation

In the original article,1 the number of steps involved in the formal total synthesis of erogorgiaene was erroneously reported. The total number of steps for this formal total synthesis should be 13. In addition, ref.4a,8a,8b were cited incorrectly. The correct citations are given below. Moreover, the synthesis of 9 should be cited as ref.6b The Authors

The analysis of two distinct strategies toward the enantioselective formal total synthesis of (+)-Gelsenicine

A formal total synthesis of dactylol

The stereoselective synthesis of deoxy C‐glycoside derivatives that have a methylene or methyl group at C‐2 position was investigated by employing the Claisen rearrangement of 2‐vinyloxy methyldeoxy‐glycals as the synthetic precursors. The method proceeded with high diastereoselectivity to afford C‐2‐methylene α‐C‐glycosides. Complementary to this protocol, a ZnII‐mediated anomerization of the α‐C‐glycosides to give the corresponding β‐C‐glycosides was also used to obtain diastereomerically pure C‐2‐methylene β‐C‐glycosides. The generality of the reaction was fully evaluated, and the developed method was successfully applied to the formal stereoselective total synthesis of (–)‐brevisamide, a monocyclic ether alkaloid that was isolated from Karenia brevis (red tide dinoflagellate).

A novel preparation of methyl (13S)‐13‐hydroxyisoatisiren‐18‐oate (4), a key‐intermediate in a synthesis of (+)‐methyl trachyloban‐18‐oate ((+)‐1), from (−)‐abietic acid, is described. Since (−)‐1 has been previously converted into (−)‐methyl 16‐oxo‐17‐norkauran‐18‐oate ((−)‐16), our preparation of 4 constitutes also a formal total synthesis, from (−)‐abietic acid, of (+)‐16. Key steps in this approach were the allene photoaddition to podocarp‐8(14)‐en‐13‐one (5) and the conversion of the endo‐toluene‐4‐sulfonate 11 into the exo‐benzoate 12b.

The formal total synthesis of the fungal GGTase I inhibitor (+)-citrafungin A 1 is described. The key steps include a selective vinyl anion addition of the anion derived from iodide 10 to the lactone 9 and lactonization/selective deprotection of the allylic alcohols 8 and 23 to afford the citrafungin lactone. Esterification with the isocitrate 6 afforded citrafungin A tetra-t-butyl ester 5 which completed the formal total synthesis.

A chirally catalysed ene reaction in a novel formal total synthesis of the antitumor agent laulimalide

The structurally unique natural product telomestatin incorporates seven oxazole rings and one sulfur-containing thiazoline in a macrocyclic arrangement. The compound is a potent inhibitor of the enzyme telomerase and therefore provides a structural framework for developing new potential therapeutic agents for cancer. An efficient formal total synthesis of telomestatin is reported in which the key steps are the use of dirhodium(II)-catalyzed reactions of diazocarbonyl compounds to generate six oxazole rings, demonstrating the power of rhodium carbene methodology in organic chemical synthesis. CD spectroscopy establishes that seco-derivatives of telomestatin are potent stabilizers of G-quadruplex structures derived from the human telomeric repeat sequence. Mass spectrometry studies, confirmed by molecular dynamics simulations, provide the first evidence that high affinity binding to terminal G-tetrads in both 1:1 and 2:1 ligand complexes is mediated through the macrocycle coordinating a monovalent cation, with selectivity for the antiparallel structure.

The formal total synthesis of elemane-type sesquiterpenoid eleman-8β,12-olide was conducted with samarium(II) iodide-induced cyclization as the key step.