Efficient Synthesis of the Pharmacophore of the Highly Potent Antitumor Antibiotic CC-1065

Abstract

The pharmacophore CPI (3) of the potent antitumor antibiotic CC-1065 (1) was synthesized in a very short reaction sequence of 11 steps with an overall yield of 23 %. The key steps are two consecutive cyclizations mediated by organotransition metal complexes, which form first the pyrroline and then the pyrrole ring in 3. Thus, halogen metal exchange of the N,N'-bisallylbromobenzene with tBuLi and subsequent reaction with Cp 2 ZrMeCl gave 11 as a single product in 60 % yield after quenching with two equivalents of iodine. Transformation of the iodomethyl group in 11 into an acetoxymethyl group, followed by Heck reaction, isomerization, and reductive cleavage, provided the pyrroloindoline system 4, which was converted into 3.

Density functional theory studies on molecular geometry, spectroscopy, HOMO–LUMO and reactivity descriptors of titanium(IV) and oxidozirconium(IV) complexes of phenylacetohydroxamic acid

“…Compared to extensively studied metal complexes scant reports describe titanium(IV) and oxidozirconium(IV) complexes 13–16 despite the fact that the chemistry of titanium and zirconium compounds has been one of the most active research areas. Literature survey reveals that numerous titanium(IV) and oxidozirconium(IV) complexes have been synthesized from ligands having hetero‐donor atoms (O, N, S) which demonstrate enhanced biological activity 17,18 …”

“…Literature survey reveals that numerous titanium(IV) and oxidozirconium(IV) complexes have been synthesized from ligands having hetero-donor atoms (O, N, S) which demonstrate enhanced biological activity. 17,18 Hydroxamic acids having general formula RC(O)N(R')OH are weak organic acids and bioactive compounds. 19 The hydroxamic acids synthesized from carboxylic acid precursors having two labile protons (O H, N H) display excellent chelating ability.…”

Mild and efficient capture and functionalisation of CO2 using silver(i) oxide and application to 13C-labelled dialkyl carbonates

“…This is of interest as, despite its apparent simplicity, methods to transform alkyl halides to the corresponding alcohols often result in elimination or require harsh reaction conditions. 51,52 The conversion of alkyl iodides to the corresponding alcohols using silver(I) salts have been previously reported and include Ag 2 O, 53,54 Ag 2 CO 3 55 and AgBF 4 . 52 The highest conversions to the unsymmetrical carbonate 2 were observed when the reactions were performed without additional solvents.…”