266323-48-2

Upstream product

• 266323-59-5 (2E,5S)-5-(4-methoxybenzyloxy)-4-oxo-2-hexenal 
• 266323-47-1 (S)-1-(2-furyl)-1-(4-methoxybenzyloxy)ethane 
• 4208-64-4 (S)-1-(2-furanyl)ethanol 
• 4208-64-4 1-(2-furyl)ethanol 

Downstream Products

• 266323-53-9 (2S,6S,9E,11R,12S)-6,12-dimethyl-2-(2-furyl)-11-(methoxymethoxy)-14-(4-methoxyphenyl)-3,7,13-trioxa-9-tetradecene-4,8-dione 
• 266323-52-8 (2S,6S,9E,11R,12S)-6,12-dimethyl-2-(2-furyl)-11-hydroxy-14-(4-methoxyphenyl)-3,7,13-trioxa-9-tetradecene-4,8-dione 
• 172923-77-2 (+)-macrosphelide A 
• 266323-51-7 (2S,6S,9E,12S)-6,12-dimethyl-2-(2-furyl)-14-(4-methoxyphenyl)-3,7,13-trioxa-9-tetradecene-4,8,11-trione 

Relevant academic research and scientific papers

Furan ring oxidation strategy for the synthesis of macrosphelides A and B

By using the convenient protocol for conversion of 2-substituted furans into 4-oxo-2-alkenoic acids ((i) NBS, (ii) NaClO2), macrosphelide B (2) was synthesized from furyl alcohol 5 (> 98% ee) and acid 6 (99% ee). The protocol was first applied to the PMB ether of 5 to afford acid 13b. On the other hand, DCC condensation of acid 6 with 5 gave 16 after deprotection of the TBS group. Condensation was again carried out between 13b and 16 to furnish the key ketone 17, which upon reduction with Zn(BH4)2 afforded anti alcohol 18 stereoselectively (15:1). After protection/deprotection steps, the furan 18 was converted to seco acid 3 by using the furan oxidation protocol mentioned above, and lactonization of 3 with Cl3C6H2COCl, Et3N, and DMAP afforded 22 (MOM ether of 2), which upon deprotection with TFA produced 2. Transformation of 22 to macrosphelide A (1) was then investigated. Although the chelation-controlled reduction of 22 should afford the desired anti alcohol 24, Zn(BH4)2 at 4 in MeOH at -15 °C produced the syn isomer 23 with > 10:1 diastereoselectivity. Mitsunobu inversion of the resulting C(14)-hydroxyl group and deprotection of the MOM group with TFA afforded 1. Similarly, reduction of 2 with NaBH4 afforded the C(14)-epimer of 1 stereoselectively. The observed stereoselectivity in the reductions of 22 and 2 could be explained on the basis of computer-assisted calculation, which showed presence of the low-energy conformers responsible for the stereoselective reduction. In addition, conversion of 2 to 1 was established, for the first time.

Total synthesis of macrosphelides B and A

An efficient total synthesis of macrosphelide B has been developed in which the C(5)-O(10) and the C(11)-O(16) fragments were prepared from (S)-1- (2-furyl)ethanol of >98% ee via oxidation of the furan part. In addition, macrosphelide B was transformed stereoselectively into macrosphelide A by reduction followed by Mitsunobu inversion. (C) 2000 Elsevier Science Ltd.