Synthesis of DEFG ring system of cneorins

Abstract

The cneorins have been isolated from the xerophytic shrub Cneorum pulverulentum, which is native to the Canary Islands. They are natural products containing a [4.3.1]propellane ring system (DEFG rings) as the northern part of the molecule and a 5,5-spiroketal unit and a butenolide moiety (A ring) as the southern part. The synthesis of the DEFG ring system of the cneorins is described. The key steps include: intramolecular cyclopropanation of a diazomalonate providing the EFG ring fragment and an anionic cyclization of a sulfone yielding the [4.3.1]propellane ring system.

A unified strategy for the total syntheses of eribulin and a macrolactam analogue of halichondrin B

“…Thus and as shown in Scheme 4 , the Nozaki–Hiyama–Kishi (NHK) reaction ( 4 ) between 33 and 8 (NiCl 2 /CrCl 2 , 47% yield, unoptimized conditions) followed by cycloetherification [1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)] afforded sulfone methyl ester 35 (via transient intermediate 34 ), which underwent smoothly the expected intramolecular displacement at the mesylate position under the basic conditions employed (81% yield), as shown in Scheme 4 . Unfortunately, however, attempts to induce the macrocyclization of p -tolylsulfone methyl ester 35 under various basic conditions [e.g., lithium diisopropylamide (LDA) ( 42 ), sodium hexamethyldisilazide (NaHMDS) ( 43 ), potassium hexamethyldisilazide (KHMDS) ( 44 ), potassium tert -butoxide (KO t -Bu) ( 45 )] failed to form the desired eribulin precursor 36 , leading us to search for an alternative approach.…”