Daurichromenic acids

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 two novel chromane derivatives rhododaurichromanic acids A and B [19] as well as the known Daurichromenic acid [20] are members of a new interesting class of anti-HIV agents and are therefore attractive synthetic targets (Scheme 3). These compounds were successfully synthesized by Z. Jin et al. [21] in good overall yields, applying a microwave-assisted tandem condensation and intramolecular S -type cyclization to form the... 

Scheme 3 Microwave-assisted synthesis of Daurichromenic Acid and Rhododaurichromanic Acids A and B...

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... 

The reaction of resorcinols with a,P-unsaturated aldehydes and ketones catalysed by ethylenediamine diacetate has been used to synthesise the naturally occurring chromenes confluentin and daurichromenic acid <05OBC3955, 05TL7539>. 2-Hydroxynaphthoquinone behaves similarly providing a useful route to pyranonaphthoquinones <05S3026>. 

Wilson and coworkers [76] approached daurichromenic acid and analogs via a similar approach. As shown in... 

Scheme 12.30, Wilson and coworkers used diketoesters 127 and the conditions of Tietze et al. [65] in the oxa-[3+3] formal cycloaddition of a variety of different aldehydes 128 to give cycloadducts 129 in excellent yields. Their DDQ aromatization also suffered in yields, although the saponification, leading to daurichromenic acid analogs 131, appeared to be effective.

The most elegant syntheses of rhododaurichromanic acid A 105a, B 105b, and of daurichromenic acid 113a were reported by Jin and coworkers [77]. Jin s synthesis features a unique microwave-assisted formal oxa-[3+3] cycloaddition of resorcinol derivatives with enals, and provides a rapid and novel approach to chromenes (Scheme 12.32). It also bypasses the DDQ aromatization that was problematic in ours [73] and in the synthesis of Wilson s [76]. Their... 

More recently, Lee et al. have developed a new methodology for the preparation of a variety of benzopyrans by using ethylenediethylenediamine diacetate-catalyzed reactions of resorcinols to a,(3-unsaturated aldehydes, and applied these reactions to the synthesis of natural products ( )-cannabichromene 112a (Scheme 12.33), ( )-cannabi-chromenic acid 145 (Scheme 12.34), ( )-daurichromenic acid 113a (Scheme 12.35), and confluentin 147 (Scheme 12.36) [78,79]. 

As shown in the Scheme 12.35, under the same reaction condition, reaction of 146 with trans,trans-famtsd 114 gave adduct 139 in 57% yield. Hydrolysis of 139 with 5 M NaOH at 80 °C for 16 h in DMSO afforded daurichromenic acid... 

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