A One-Pot Condensation of Pyrones and Enals. Synthesis of 1H,7H-5a,6,8,9-Tetrahydro-1-oxopyrano[4,3-b][1]benzopyrans

Abstract

Condensation of various 6-substituted 4-hydroxypyrones 1 with 1-cyclohexenecarboxaldehydes in the presence of L-proline in ethyl acetate gave high yields of substituted 1H, 7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyrans. The reaction presumably occurs via the 1,2-addition of the pyrone with the aldehyde followed by dehydration and then cyclization through a 6Π electrocyclic process. A remarkable asymmetric induction was obtained from a stereogenic center (C4) of the cyclohexenecarboxaldehyde [such as (S)-perillaldehyde] to provide only the C5a,7-trans tricyclic pyrone products. On the other hand, condensation of 3-(formyloxy)-or 3-hydroxy-2-methyl-1-cyclohexenecarboxaldehydes with pyrones 1 gave mixtures of C5a,6-cis and -trans products. Several of the tricyclic pyrones strongly inhibit acetylcholinesterase activity, DNA synthesis, and tumor cell growth in vitro.

Asymmetric electrocyclic reactions

“…For small R 1 groups, it was proposed that equilibration between axial and equatorial substituents should favor the intermediate with minimum A 1,3 strain, and equatorial approach of the oxygen atom during the ring closure would lead to the major isomer. Similar transformations with other electrophiles have been reported, [168][169][170][171] and an approach in which the source of chirality is carbohydrate-derived has also been described. 172 8p Electrocyclizations ( p 8 a ) 8p/6p Electrocyclization cascades.…”

Combining the rapid MTT formazan exocytosis assay and the MC65 protection assay led to the discovery of carbazole analogs as small molecule inhibitors of Aβ oligomer-induced cytotoxicity

“…1. The focused library of tricyclic pyrones was prepared according to our published procedures (Hua et al, 1997;Hua et al, 2003).…”

A Formal [3 + 3] Cycloaddition Approach to Natural‐Product Synthesis

“…First, sterically congested α,β-unsaturated iminium salts such as 13 can impede the formal [3 ϩ 3] cycloaddition, although Jonassohn's [12] work provides some assurance. Secondly, and more significantly, despite reports by Jonassohn [12] and Hua, [13] as well as our own results, [16] the ability to control the stereochemistry of the angular methyl group at C-6a through this key formal [3 ϩ 3] cycloaddition reaction was quite speculative. Scheme 10 However, because the 6π-electron electrocyclic ring-closure of the respective 1-oxatriene 55 was found to be reversible, [15,22] a favorable diastereoselectivity could be achieved leading to the thermodynamically more stable isomer 12, in which the C-6a methyl group is in the β-position (Scheme 10).…”

“…Subsequently, Hua reported an elegant study [13] that preceded our communication. [11,14] In their study, shown in Scheme 5, cyclic enals were employed in view of their inter- www.eurjoc.org est in arisugacin A (6).…”

“…[68] The formal oxa-[3 ϩ 3] cycloaddition of enal 143, derived from aldehyde 141, with hydroxynaphthoquinone 144 under Hua's conditions [13] led to pyranonaphthoquinone 145 in 54% yield as a single regioisomer (Scheme 32). Interestingly, the undesired regioisomer that can arise from 147 was not seen.…”