The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′‐epi‐Leucophyllidine

Abstract

Supporting information for this article is given via a link at the end of the document.

Enantioselective Total Synthesis of (+)‐Eucophylline

“…The HPLC analysis confirmed the high enantiomeric excess of the natural product (98 % e.e.). 1D NMR ( 1 H, 13 C, and 13 C DEPT-135) and 2D NMR spectroscopic data ( 1 H-1 H COSY, 1 H-13 C HSQC, and 1 H-13 C HMBC) were in good agreement with those reported in the literature for the natural product [1] and synthetic samples, [4,6,7] although a slight shift in some 1 H NMR signals (see Supporting Information, Figures S10-S11 and Tables S12-S16) were observed, which may be attributed to hydrogen bonding in methanol-d 4 and also to the amphoteric nature of eucophylline 1. The specific optical rotation value of synthetic (+)-1 ([α] D 25 = + 72.16 (c = 0.53, MeOH)) was also found to be higher than that of the natural product ([α] D 27 = + 27 (c = 0.75, MeOH).…”

“…Recent investigations by Stoltz and co-workers directed toward the same goal resulted in the synthesis of 1 and that of the 16'epimer of leucophyllidine 2. [6] The first total synthesis of (+ /À )-Eucophylline 1 in 10 steps and 10 % overall yield was reported by our laboratory back in 2015, [7] relying on a 3-component free-radical olefin carbooximation. [8] Since then, two enantioselective total synthesis have been reported by Pandey et al, [4] and more recently by Stoltz and co-workers.…”

“…[8] Since then, two enantioselective total synthesis have been reported by Pandey et al, [4] and more recently by Stoltz and co-workers. [6] The former group disclosed a 21 steps synthesis of 1 starting from N-protected piperidinone 4, based on the elaboration of their key-fragment 5, accessible through a Johnson-Claisen rearrangement, [9] giving access to both enantiomers of 5 in a straightforward manner (Scheme 1). Stoltz's strategy [6] relied on the enantioselective decarboxylative allylic alkylation of intermediate 6 (itself available from valerolactam in 2 steps), [10] that was rapidly converted into fragment 7 in high yield and enantioselectivity on a large scale.…”

“…[6] The former group disclosed a 21 steps synthesis of 1 starting from N-protected piperidinone 4, based on the elaboration of their key-fragment 5, accessible through a Johnson-Claisen rearrangement, [9] giving access to both enantiomers of 5 in a straightforward manner (Scheme 1). Stoltz's strategy [6] relied on the enantioselective decarboxylative allylic alkylation of intermediate 6 (itself available from valerolactam in 2 steps), [10] that was rapidly converted into fragment 7 in high yield and enantioselectivity on a large scale. In both approaches, the quinoline skeleton was then elaborated through the coupling between the respective chiral piperidines Structures of some alkaloids found in Leuconotis eugenifolius.…”

Asymmetric Total Syntheses of Schizozygane Alkaloids

“…We then turned our attention to prepare chiral 15a and 15b for asymmetric syntheses of schizozygane alkaloids. As depicted in Scheme , starting with tryptamines 20a and 20b , coupling with the known compound 21 provided high yields of 22a and 22b , which were transformed to imines 23a and 23b , respectively, under the classic Bischler–Napieralski cyclization conditions. , Initial efforts to prepare chiral 13a by a transfer hydrogenation with Noyori–Ikariya catalyst were fruitless . Gratifyingly, reduction of 23a and 23b using a chiral sodium triacyloxyborohydride, which was simply prepared by mixing NaBH 4 with proline 24 , provided 25a and 25b , respectively, with good enantiopurities .…”