One-Pot Eschenmoser Episulfide Contractions in DMSO: Applications to the Synthesis of Fuligocandins A and B and a Number of Vinylogous Amides

Abstract

Practical total syntheses of the natural products fuligocandin A (2a) and fuligocandin B (3) have been achieved through a convergent strategy depending on the Eschenmoser episulfide contraction as a key step. Conducting the reaction in DMSO proved to be an efficient and general method for the synthesis of a variety of vinylogous amides, such as azepan-2-ylidenepropan-2-one.

The Eschenmoser coupling reaction under continuous-flow conditions

“…Since these early days the Eschenmoser coupling has been applied many times as a useful reaction step in a variety of synthesis strategies. Different natural products, such as diplodialid macrolactone- [5], sedamine alkaloid- [6], sparteine- [7], mersicarpine- [8], batzelladine- [9], fuligocandin- [10] and vitamin B12-derivatives [11] were prepared with the aid of sulfide contraction steps. Pharmaceutically important substances, such as methylphenidat [12] or the marine neurotoxin hemibrevetoxin [13], were prepared by utilization of the Eschenmoser coupling reaction.…”

Facile Synthesis of Naphtho[2,3‐d]thiazoles, Naphtho[2,3‐e][1,3,4]thiadiazines and Bis(naphtho[2,3‐d]thiazolyl)copper(II) Derivatives from Heteroylthiosemicarbazides

“…In this paper, we decided to employ the coupling method developed by Eschenmoser and co-workers for the extrusion of sulfur from organic thiones and related systems. [22][23][24][25] Treatment of 1a -1f with 2,3-dichloro-1,4-naphthoquinone 2 (related to α-haloketones) (Scheme 1) yielded thioiminium salts 6. Refluxing the latter with triethylamine as a base and triphenylphosphine as thiophilic reagent, sulfur was not extruded and the expected naphthoxadiazepines 8 or benzindazoles 9 were not formed, instead, products 3 -5 could be isolated (Scheme 1).…”

Intramolecular Azide to Alkene Cycloadditions for the Construction of Pyrrolobenzodiazepines and Azetidino-Benzodiazepines

“…The N-(2'-azidobenzenesulfonyl)-2-ethenylpyrrolidine (15) (125 mg, 0.449 mmol) was dissolved in toluene (10 mL) and heated to reflux for 18 h. The reaction was allowed to reach room temperature before the solvent was removed and the crude was purified by silica chromatography (25 g) (EtOAc/Hex;2:3) to yield the aziridine product 17 as a tan colored oil (50 mg, 44%). NMR: δH (500 MHz, CDCl3): 1.81-2.07 (4H, m, 2 × CH2), 2.91-2.95 (1H, m, SO2NCHH), 3.32 (1H, dd, J = 9.9, 11.7, ArNCHH), 3.50 (1H, m, SO2NCHH), 3.57 (1H, dd, J = 3.9, 11.7, ArNCHH), 3 …”

“…The pyrrolobenzodiazepines (PBDs), of which the natural products abbeymycin (1), DC-81 (2) and fuligocandin B (3) (Figure 1) are typical examples, are a class of molecule that has attracted significant OPEN ACCESS interest due the antitumour and antibiotic activity of several members [1][2][3][4][5]. Synthetic hybrids [5][6][7][8] and dimers [5,[9][10][11] have also shown significant biological activity and members of the dimer class have entered Phase II clinical development as antitumour compounds.…”