Furan Ring Oxidation Strategy for the Synthesis of Macrosphelides A and B

Abstract

By using the convenient protocol for conversion of 2-substituted furans into 4-oxo-2-alkenoic acids ((i) NBS, (ii) NaClO(2)), 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(BH(4))(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 Cl(3)C(6)H(2)COCl, Et(3)N, 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(BH(4))(2) at <-90 degrees C gave a 2 approximately 1:1 mixture of anti/syn alcohols. On the contrary, reduction with NaBH(4) in MeOH at -15 degrees 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 NaBH(4) 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.

Furan‐Oxidation‐Triggered Inducible DNA Cross‐Linking: Acyclic Versus Cyclic Furan‐Containing Building Blocks—On the Benefit of Restoring the Cyclic Sugar Backbone

“…[7] Notwithstanding these toxic effects, furan has been identified as representing a caged reactive functionality and seems to be an ideal template for the mild and selective generation of a reactive intermediate on demand. This furan-ring oxidation principle and the idea of using an easily incorporated and stable aromatic furan moiety as a substitute for a reactive unit has been elegantly used in the total synthesis of macrosphelides A and B [8] and (+)-Aspicillin. [9] The principle was further applied in a combinatorial process for the generation of a large library of distinct molecular skeletons starting from a common 2-alkoxyfuran building block.…”

A concise diastereoselective synthesis of 5′-epi synargentolide-B

“…8 Then, protection of secondary alcohol as TBS-ether 6 (TBDMSCl, imidazole, DCM) followed by the NBS-promoted furan oxidation of 6 under basic conditions, resulting in the desired g-keto a,b-unsaturated aldehyde 7, at an excellent yield (88%, after two steps). 9 The aldehyde 7 was subjected to Wittig olefination to give the keto conjugated unsaturated ester 3 at a yield of 90% with a 20:1(E:Z) ratio. The reduction of 3 under Luche conditions 10 delivered the expected syn diol 8 with a 97:3 diastereomeric ratio (as judged by the 1 H NMR spectra) at a yield of 88%.…”

Simple Biocatalytic Access to Enantiopure (S)‐1‐Heteroarylethanols Employing a Microbial Hydrogen Transfer Reaction

“…[22] A screening to obtain this building block from the corresponding ketone 7a by biocatalytic hydrogen transfer revealed, that R. ruber DSM 44540, DSM 44541 and R. ruber DSM 43338 (Table 3, entries 6, 12, 11) gave the highest conversion and best enantiomeric purity of alcohol (S)-7b. Interestingly, some strains showed higher selectivity and activity for 3-acetylthiophene 5a as compared to 2-acetylfuran 7a (entries 9 ± 11), and vice versa (entry 6, activity; entry 3: selectivity), no clear trend was observable.…”