First total synthesis of antihypertensive natural products S-(+)-XJP and R-(−)-XJP

Abstract

The first asymmetric total synthesis of antihypertensive natural products S-(+)-XJP and R-(-)-XJP has been achieved in 8 steps starting from commercially available 6-bromo-2-hydroxy-3-methoxybenzaldehyde. Key steps included intramolecular Heck reaction and oxidative ozonolysis reaction with the retention of stereochemistry. A latent functionality strategy was implemented to circumvent the racemization in this endeavor. The protocol described here provided a fast and easily accessible synthetic method to obtain optically pure isochroman-4-one derivatives. Furthermore, the in vivo antihypertensive effects of (±)-XJP, S-(+)-XJP and R-(-)-XJP were investigated on spontaneously hypertensive rats. The obtained results could provide valuable information to identify a promising lead for further chemical modification research.

An Oxyboration Route to a Single Regioisomer of Borylated Dihydrofurans and Isochromenes

“…For 28′, 1 H NMR (CDCl 3 , 600 MHz): δ 6.99 (d, J = 1.9 Hz, 1H), 6.91 (d, J = 2.0 Hz, 1H), 4.64 (d, J = 6.4 Hz, 2H), 3.87−3.84 (m, 6H), 2.12−2.08 (m, 1H), 2.04 (s, 3H). 13 7,8-Dimethoxy-3-methylisochroman-4-one (29). First, intermediate SI-11 was prepared according to general procedure E (see SI) to generate the mixture of 28 and 28′ (0.130 g, 0.400 mmol, 1.0 equiv) (with the exception that no isolation was performed).…”

“…Similarly, isochromenes are common cores in biologically active compounds, including natural products and pharmaceuticals. − Due to their ubiquity, ,,− developing synthetic methods from simple and readily available starting materials has been the focus of ongoing research. ,, …”

An efficient synthesis of 4-isochromanones via Parham-type cyclization with Weinreb amide

“…(±)-XJP was a structurally unique 4-isochromanone compound recently isolated from the peel of Musa sapientum L., and was endowed with potent antihypertensive activity. Although the total synthesis has been achieved via different synthetic routes, the overall yield were not satisfying 17,[28][29] . Herein, we would like to report the synthesis of the (±)-XJP via the new explored methodology (Scheme 2).…”

New Perspectives in the Indole Ring Functionalization using 2‐Indolylmethanols

“…[3] Structural implementation of 3-substituted indoles 1 bearing a suitable leaving group at the benzylic position can be readily made by exploiting the formation of alkylideneindolenine species 2 and 3 (Scheme 1). [4] Removal of the leaving group from these substrates can be realized under acidic or basic conditions leading to neutral alkylideneindolenine 2 or the more reactive cationica nalogue 3. [5] These intermediates act as vi-nylogous imino derivatives allowing for the subsequent nucleophilic addition leading to the target functionalized indole.D espite of the presence of two electrophilic sitesi ni ntermediate 3 (resonance structures 3a and 3b), attack by the nucleophilic reagento ccurs exclusively at the exocyclic carbon thus enabling the immediate restoration of the ring aromaticity.…”