Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Org Biomol Chem. 2013 May 21;11(19):3187-202. doi: 10.1039/c3ob40205c. Epub 2013 Apr 8.
The transannular iodoamination of substituted 1,2,3,4,7,8-hexahydroazocine scaffolds has been developed into a versatile, diastereodivergent route to enable the synthesis of a range of pyrrolizidine alkaloids, as demonstrated by the syntheses of (-)-hyacinthacine A1, (-)-7a-epi-hyacinthacine A1, (-)-hyacinthacine A2, and (-)-1-epi-alexine. The requisite 1,2,3,4,7,8-hexahydroazocines (bearing either an N-α-methyl-p-methoxybenzyl group or no N-substituent) were readily prepared via conjugate addition of lithium (R)-N-but-3-enyl-N-(α-methyl-p-methoxybenzyl)amide to either tert-butyl (4S,5R,E)-4,5-dihydroxy-4,5-O-isopropylidene-2,7-dienoate (derived from d-ribose) or tert-butyl (S,S,E)-4,5-dihydroxy-4,5-O-isopropylidene-2,7-dienoate (derived from l-tartaric acid) coupled with in situ enolate oxidation with (-)-camphorsulfonyloxaziridine, followed by ring-closing metathesis with Grubbs I catalyst. Subsequent reaction with I2 resulted in transannular iodoamination (accompanied by concomitant loss of the N-α-methyl-p-methoxybenzyl group for tertiary amine substrates) to give the corresponding pyrrolizidine scaffolds.
取代的 1,2,3,4,7,8-六氢氮杂卓骨架的跨环碘胺化已发展成为一种通用的、立体化学发散的途径，可用于合成一系列吡咯里西啶生物碱，这一点已通过（-）-百合碱 A1、（-）-7a-表百合碱 A1、（-）-百合碱 A2 和（-）-1-表阿列辛的合成都得到了证明。所需的 1,2,3,4,7,8-六氢氮杂卓（带有 N-α-甲基-p-甲氧基苄基基团或没有 N-取代基）可通过（R）-N-丁-3-烯基-N-（α-甲基-p-甲氧基苄基）酰胺与叔丁基（4S,5R,E）-4,5-二羟基-4,5-O-异丙叉基-2,7-二烯酸酯（衍生自 d-核糖）或叔丁基（S,S,E）-4,5-二羟基-4,5-O-异丙叉基-2,7-二烯酸酯（衍生自 l-酒石酸）进行共轭加成来轻易制备，这两种物质与（-）樟脑磺酸氧杂环丁烷原位烯醇氧化偶联，然后用 Grubbs I 催化剂进行闭环复分解反应。随后与 I2 反应导致跨环碘胺化（伴随伴随叔胺底物中 N-α-甲基-p-甲氧基苄基基团的同时消除），得到相应的吡咯里西啶骨架。
