Alkaloids from the Fruits of Stephania japonica, 3. Structures of Prostephanaberrine and Stephanaberrine, Two New Hasubanan Alkaloids

The genus Stephania (Menispermaceae): Chemical and pharmacological perspectives

“…(16), aknadine, 16-oxoprotometaphanine, aknadinine (15), cyclanoline, cycleanine (28), d-fangchinoline (50), oxostephabenine (52), stephabenine (53), lanuginosine (54), epistephanine, dehydroepistephanine, d-tetrandrine (18), trilobine, epistephamiersine, insularine, hasubanonine, hernandoline, obamegine, homoepistephanine, steponine, stephasunoline, oxostephasunoline (55), homostephanoline, hypoepistephanine, isochondrodendrine, oxostephamiersine, isotrilobine, l-quercitol, metaphanine, n-nor-1, 2-dehydroepistephanine, oxostephanine, plastoquinone, protostephanaberrine, prometaphanine, stepinonine, stebisimine, oxostephasunodine, stephanaberrine, stephanine (6), prostephanaberrine (56), stephamiersine, stephanoline, stepholine, stepisimine, viburnitol, protostephanine (57), oxoepistephamiersine (58), oxostephamiersine, stephadiamine (Inubushi and Ibuka, 1977;Matsui et al, , 1973Matsui et al, , 1982aMatsui et al, 1975;Kondo et al, 1983;Taga et al, 1984;Yamamura and Matsui, 1985;Matsui and Yamamura, 1986;Duke, 1992;Hall and Chang, 1997) and bebeerine (59) (Hullatti and Sharada, 2010).…”

Development of Enantioselective Synthetic Routes to the Hasubanan and Acutumine Alkaloids

“…As observed for related alkaloids, − we found that (−)-prostephanaberrine ( 18 ) exists as a solvent-dependent mixture of ring and chain isomers (ratio of 18 : 121 = 5:1 in chloroform- d ). Hydrolysis of (−)-prostephanaberrine ( 18 , aqueous hydrochloric acid, 50 °C) cleanly afforded (−)-stephanaberrine ( 19 ) in 65% yield . Benzoylation of (+)- N , O -dimethylstephine ( 13 , benzoyl chloride) furnished (−)-stephabenine ( 12 ) in 74% yield (Scheme B).…”

“…Synthetic (−)-prostephanaberrine ( 18 ) exists as a solvent-dependent mixture of ring and chain isomers (ratio of 18 : 121 = 5:1 in chloroform- d ). Natural (−)-prostephanaberrine ( 18 ) is reported to exist only in the chain form 18 in chloroform- d . This isolation report for natural (−)-prostephanaberrine ( 18 ) notes that natural (−)-prometaphanine, (−)-prostephabyssine, and (−)-16-oxoprometaphanine, alkaloids differing from (−)-prostephanaberrine ( 18 ) by aromatic substitution pattern, each exist as a solvent-dependent equilibrium mixture with the corresponding hemiketal: R f = 0.43 (5% methanol–dichloromethane; UV, CAM).…”

“…We have developed a general and versatile strategy to access the hasubanonine and stephamiersine classes of hasubanan alkaloids, and applied this strategy to the syntheses of (−)-hasubanonine ( 1 ), (−)-runanine ( 2 ), (−)-delavayine ( 3 ), and (+)-periglaucine B ( 8 ). , We also modified this approach to access (−)-acutumine ( 4 ) and (−)-dechloroacutumine ( 5 ). , Here we disclose the development of this synthetic strategy and the adaptation of this work to the first enantioselective syntheses of six additional hasubanan alkaloids: (−)-stephabenine ( 12 ), (+)- N , O -dimethylstephine ( 13 ), , (+)- N , O -dimethyloxostephine ( 14 ), (+)-oxostephabenine ( 15 ), (−)-prostephanaberrine ( 18 ), and (−)-stephanaberrine ( 19 ), which comprise the remaining unaddressed oxostephausoline and metaphanine classes of hasubanan alkaloids. We also broaden the strategic application of 5-(trimethylsilyl)cyclopentadiene ( 36 ) in complex molecule synthesis by demonstrating the site-selective functionalization of unsaturated carbon–carbon bonds in the presence of the norbornene substructure of the silylcyclopentadiene adducts.…”

Substrate-Modified Functional Group Reactivity: Hasubanan and Acutumine Alkaloid Syntheses

“…Hasubanan alkaloids of varying oxidation states were then accessed from the tetracycle 21 . Mukaiyama hydration of 21 , followed by in situ acid-mediated cyclization, afforded (+)-periglaucine B ( 22 ), which served as a precursor to six additional alkaloids ( 23 – 26 , 28 , and 29 ). − …”