Daurichromenic acid ester

The highly potent anti-HIV natural product daurichromenic acid (10-100) was synthesized by Jin and coworkers [36] using a microwave-assisted reaction of the phenol derivative 10-97 and the aldehyde 10-98 (Scheme 10.25). Normal heating gave the desired benzo[b]pyran 10-99 by a domino condensation/intramolecular SN2 -type cyclization reaction only in low yield. However, when the reaction mixture was irradiated twenty times in a microwave for 1-min intervals, 10-99 was obtained in 60% yield. This compound was then transformed into 10-100 by cleavage of the ester moiety. 

The mixture gave only a 15% yield of the desired product after refluxing for 4 days. The yield was improved to 32% when the mixture was heated at 90 °C in a sealed tube for 1 day. As the intramolecular S -type cycli-zation is believed to be fast, the overall slow reaction is presumably due to the high activation energy in the condensation step. Therefore, the authors tried microwave irradiation, applying a domestic microwave oven. This resulted in a dramatic increase of the rate and the yield (70%) of the reaction. Optimized conditions were found to be microwave irradiation of a mixture of the ethyl ester (1 equiv) with the aldehyde (2.0 equiv) for 20 x 1 min, after which time an additional 1.0 equiv of the aldehyde was added and the mixture was irradiated again for 20 min. As the hydrolysis of the ethyl ester moiety to Daurichromenic acid proved to be extremely difficult, the authors switched to the application of a /i-lrimethylsilyl ethyl ester, which... 

After total synthesis of rhododaurichromanic acid by photochemical [2+2] cycloaddition, inspired by the precedents in polyene cyclizations, especially the work of Omura and coworkers [74], we attempted to treat daurichromenic ester 118a with various Lewis acids and mercury reagents but failed, as shown in Scheme 12.28. Fortunately, the outcome changed when using Brpnsted acids such as TFA, especially when it was used at 30 equiv or as a cosolvent with CH2CI2, we isolated two products 121 and 122 with each as a single diastereomer, the formation of 122 likely proceeds through the classic polyene cyclization via 123 [75]. 

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