Novel Phosphorus Radical-Based Routes to Horsfiline

Abstract

[reaction: see text]. Radicals derived from the phosphorus reagents, ethylpiperidine hypophosphite (EPHP) and diethylphosphine oxide (DEPO), are used in two related approaches to synthesis of the alkaloid horsfiline (1). In particular, DEPO proves beneficial for effecting cyclizations at 80 degrees C that are difficult or impossible with Bu(3)SnH.

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…58 Two novel approaches to spiroindolin-2-one alkaloid horsfiline 112, obtained from the roots of Horsfieldia superba, 61 have been performed by radical cyclization using ethylpiperidine hypophosphite (EPHP) and diethylphosphine oxide (DEPO) as the key step. 62 The 2-iodoanilide 115 derived from 113 was treated with EPHP and AIBN to give the cyclized product 116 (Scheme 18). Total synthesis of 112 was completed by removal of the protecting groups from 116 and reductive N-methylation.…”

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

“…The generic substrate 18 was loosely designed based on the original substrates 1 by swapping the locations of the radical precursor (halide) and the radical acceptor (ene-sulfonamide). The expected products of these reactions, imines like 19 , could possibly be used to make spirocyclic oxindole natural products like coerulescine [ 18 ], horsfiline [ 19 – 23 ] and elacomine [ 24 ] (whose structure is shown in Fig. 4 ).…”

Crystal structure of 1-ethyl-5-iodoindolin-2-one

“…Indolinone derivatives play an important role in the pharmaceutical industry and some of them show antineoplastic (Cane et al, 2000), antibacterial (Kumar et al, 2013) and anti-inflammatory (Mammone et al, 2006) activities. The indolinone skeleton can be also found in many known bioactive drugs, such as horsfiline (Murphy et al, 2005), rhynchophylline (Deiters et al, 2006) and the gelsemium alkaloids (Kitajima et al, 2006). In addition, indolinone derivatives are widely used in the spice industry and agriculture, as functional materials (Ji et al, 2010) and dye intermediates.…”