Biomimetically Inspired Total Synthesis and Structure Activity Relationships of 1-O-Methyllateriflorone. 6π Electrocyclizations in Organic Synthesis

Abstract

The total synthesis of 1-O-methyllateriflorone (2) is described. The construction of the cage-like domain of the molecule involved a biomimetic Claisen/Diels-Alder cascade, whereas the novel spiroxalactone framework was generated by an intramolecular Michael reaction within precursor 16a involving the carboxylate residue as the nucleophile. This finding might bear on the biosynthetic pathway by which nature forms lateriflorone. Described herein is also an interesting cascade sequence involving facile 6 pi electrocyclizations which leads to complex benzopyran systems. The biological evaluation of a small library of lateriflorone analogues and related systems establishing the first SAR within this class of compounds is also included. Among the most active compounds against tumor cells are 2, 16b, 56, 58, and 59.

Synthesis of Xanthones: An Overview

“…The total synthesis of 1-O-methyllateriflorone (144) (Fig. (11)), a xanthonoid structurally related to the previously mentioned compounds (120-124) was described by Nicolaou et al with an interesting cascade sequence involving facile 6π electrocyclizations leading to the complex benzopyran system [177]. However, Tisdale et al have previously achieved a regioselective synthesis of the tricyclic core of lateriflorone (145) (Fig.…”

“…common xanthonoid ring system, such as in the case of forbesione (120), desoxygaudichaudione (121), desoxymorellin (122), morellin (123), and gambogin (124) natural products represented in Table 2 [177]. The total synthesis of 1-O-methyllateriflorone (144) (Fig.…”

Total Synthesis of Hispidulin and the Structural Basis for Its Inhibition of Proto-oncogene Kinase Pim-1

“…Treatment of 2,4,6-trihydroxybenzaldehyde (12) with chlorodimethyl ether (MOMCl) gave the tris(methoxymethoxy)-protected compound 13. 24 Baeyer−Villiger oxidation followed by basic hydrolysis 25 27 At room temperature, the reaction of compound 17 with MOMCl preferentially afforded 4,6-bis(methoxymethoxy)-protected 18b over the desired 2,4-bis(methoxymethoxy)-protected 18a due to steric hindrance. The two compounds 18a and 18b could be distinguished based on NOESY correlations of H-5 and C3-OMe ( Figure 2) and their HMBC data (Supporting Information).…”

Polyprenylated Phloroglucinols and Xanthones

“…Quite recently, the Nicolaou group has reported a synthesis of C11-methyllateriflorone (178) (Scheme 12.29) [130]. Key to the strategy was the coupling of orthogonally protected hydroquinone 173 with acid 174 that after selective deprotection of the C7 MOM ether produced compound 175 (61% combined yield).…”