Resorcylic acid synthesis

Resacetophenone, 21,103 Resorcinol, 21, 23, 103 27, 21 cx-Resorcylic acid, 21, 27 Ring opening by hydrolysis with barium hydroxide, 22, 91 Rosenmund synthesis, aldehyde, 21, 84, 110... 

The synthetic sequence involving formation of a thioether, oxidation to the corresponding sulfone and the RBR need not be performed consecutively, although it almost invariably is when applied to the synthesis of complex targets. An example in which divorcing the sulfone preparation from the RBR was actually beneficial to the synthetic strategy is seen in the total synthesis of the resorcylic acid macrolactone (RAL) aigialomycin D by Harvey and coworkers. ... 

In solution, 3-(9-anthracenyl)-l-(pyridin-4-yl)propen-l-one undergoes (E) to (Z)-photoisomerization, whereas 3-(9-anthracenyl)-l-(pyridin-4-yl)propen-3-one does not. The driving force for the reaction is intramolecular 7i-stacking of the pyridine and anthracene rings.Photoisomerization of the ( )-enone moiety in 14-membered macrolactones leads to the (Z)-enone (40). This process has been applied to the synthesis of resorcylic acid lactones. ... 

Details for the synthesis of a resorcylic acid lactone (413) incorporating a trans-enone and an amide in the macrocyclic ring have been desrcibed. The key step of this synthesis included intermolecular olefination reaction of the aldehyde (410) with phosphonate (411) which led to isolation of the ( )-enone (412). The complete removal of MOM and Boc groups from (412) followed by lactamisation gave the desired lactam... 

An additional method of ACEC synthesis was based on hydroxybenzoic acids as the starting materials [32]. The synthesis starts from esterification of the acid with 3-cyclohexenyl-1-methyl alcohol. The following hydroxybenzoic acids were used 2-hydroxybenzoic (salicylic), 2,4-di-hydroxybenzoic ( 3-resorcylic) and 3,4,5-trihydroxybenzoic (gallic) acid. The phenolic hydroxyls in the cy-clohexenylmethyl esters were transformed in glycidyl ethers in the usual way (reaction with excess ECH followed by dehydrochlorination). Eventually, epoxidation with PAA was carried out (Scheme 51). The epoxide groups content in the ACECs thus prepared was above 85% of the calculated value. 

In 2002, Lett et al. published a convergent stereospecific synthesis of the resorcylic macolactone LL-Zl 640-2 (567) (Scheme 9.13) and hence hypothemycin (481) 382, 383). They started with the preparation of the three building blocks, 551, 555 (Scheme 9.11), and 564 (Scheme 9.12). Methyl ester 551 was produced from 4-methoxysalicylic acid (549) in four steps. Reaction of alkyne 552 with enantiopure (/ )-propylene oxide 490 afforded chiral alkyne 553, which then was converted into (Z)-vinyl iodide 555. 

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