Studies on the Narciclasine Alkaloids:  Total Synthesis of (+)-Narciclasine and (+)-Pancratistatin

Abstract

Enantioselective total syntheses of the antitumor alkaloids, (+)-narciclasine and (+)-pancratistatin, are reported. These syntheses feature a stereo-and regiocontrolled aryl enamide photocyclization to construct a common, advanced intermediate possessing a trans-fused BC substructure. Differential functional group interchange in the C-ring of this phenanthridone core structure allows for the production of the two target natural products in enantiomerically pure form.

Preparation of the First Bench‐Stable Phenyl Selenolate: an Interesting “On Water” Nucleophilic Reagent

“…Ͼ 300°C), air-stable for several days. These selenolates were fully characterized by 1 H, 13 C and 77 Se NMR spectroscopy, and the latter proved particularly diagnostic for the presence of an Se-Zn bond (δ = -41 ppm for 3 and δ = -28 ppm for 4).…”

“…[11] Recently, β-hydroxy selenides were also widely used for the synthesis of some important natural compounds. [12][13][14][15][16] Several selenium anions can be used for this purpose like (phenylseleno)silanes, [17] aluminium selenolates, [18] selenoboranes, [19] benzeneselenol in the presence of alumina [20] and selenostannanes. [21] All these reagents are relatively unstable, and they should be prepared "in situ" under controlled anhydrous conditions.…”

Chemistry and Synthesis of Highly Oxygenated Alkaloids from Amaryllidaceae: Lycoricidine, Narciclasine, Pancratistatin and Analogs

“…The photocyclization of enamide [131] was used by Rigby and coworkers in the first total synthesis of (+)-narciclasine [132] and in the synthesis of (+)-pancratistatin [133]. Preliminary studies using simple C-ring precursor established the validity of the cyclization process, which gave the required trans arrangement [134].…”

Ceric ammonium nitrate oxidation of N-(p-methoxybenzyl)lactams: competing formation of N-(hydroxymethyl)δ-lactams

“…The p-methoxybenzyl (PMB) group is often used for the N-protection 1 of amides, lactams and aza-heterocycles in the synthesis of natural [2][3][4][5][6][7][8][9][10][11][12] and non-natural products [13][14][15][16][17][18][19][20][21][22][23] because of its ease of removal. Many methods, such as Lewis 24 and Brönsted acid 18,22,[25][26][27] -mediated hydrolysis, benzylic anion oxidation, 12,28,29 catalytic hydrogenation, 30 and persulfate-mediated oxidative cleavage, 31 have been employed for the removal of the N-PMB group.…”

“…Many methods, such as Lewis 24 and Brönsted acid 18,22,[25][26][27] -mediated hydrolysis, benzylic anion oxidation, 12,28,29 catalytic hydrogenation, 30 and persulfate-mediated oxidative cleavage, 31 have been employed for the removal of the N-PMB group. Nevertheless, the most widely used method for deprotection involves the oxidative cleavage of the N-PMB moiety using ceric ammonium nitrate (CAN).…”