Synthetic Chemistry of Halichlorine and the Pinnaic Acids

Expedient Route to an Amine Precursor of Halichlorine and Pinnaic Acid from Nitrocyclopent-1-ene

“…Alternatively, nickel boride, generated in situ from sodium borohyride and nickel chloride, delivers simultaneous reduction of the alkene and nitro group in good yield (not shown). In summary, this communication describes an expedient strategy that converts nitrocyclopent-1-ene into amine precursors A (Scheme 1) of halichlorine (1) and pinnaic acid (2) in five steps. This route involves an uncommon example of an amine-catalysed conjugate addition to an internal nitroalkene that proceeds with good syn-diastereo- selectivity pertinent to the target natural products.…”

“…The breadth of activity in this area, including significant total syntheses, 1 was comprehensively summarised in 2005. 2 Subsequent reports of further total synthetic routes 3 and innovative approaches 4 to the spirocyclic quinolizidine core reflect the persistent value of routes to this target.…”

Modular Asymmetric Synthesis of Functionalized Azaspirocycles Based on the Sulfoximine Auxiliary

“…They have attracted considerable attention in the synthetic chemistry community and have recently been the topic of a specific review and a large number of reports describing efforts to synthesize them. 6 In 1999, DANISHEFSKY and co-workers published the first asymmetric total synthesis of halichlorine and pinnaic acid. 8,9 It is so far the only one for halichlorine.…”

“…In 1996, UEMURA and co-workers isolated a novel marine alkaloid from the sponge Halichondria okadai in Japanese waters. 6 Halichlorine 4 ( Figure 6) was shown to inhibit the induced expression of VCAM-1 (vascular cell adhesion molecule-1) at IC 50 7 µg.mL -1 .…”

A Concise and Flexible Synthesis of the Core Structure of Pinnaic Acid

“…4,5 In an effort to develop a synthetic strategy that could be applied to the synthesis of all members of the 6-azaspiro [4.5]decane family of alkaloids and analogues, in racemic fashion, we have investigated an approach to core structure 4 that centres on the use of spirocyclic nitrone 5 as a key intermediate.…”