Lycopodium Alkaloids: Part Viii. New Alkaloids From Jamaican Lycopodium Species

Abstract

Four more alkaloids have been isolated from Lycopodium jawcettii. Lycoditle and des-Smethyl-a-obscurine have been found in other Lycopodiunz species but base L, CIaH31N04, apd base R, are new. Some transformations of base L are described including sts conversion to the previously described base 0. . An unstable base from L. clavatum has been characterized as the picrate C I S H~~S O~. C~H~N~O~. Further characterization of the two bases fawcettidine (base F) and fawcettimine (base A) is reported.Many alkaloids have been reported (1 (a,b)) from L. fawcettii; most of these possess the lycopodine (2) type of skeleton, although neither lycopodine itself nor any of its simple relatives (those with one or no oxygen functions) have been isolated. Three bases have more recently been isolated from this Jamaican plant, all of which contain two nitrogen atoms. Two of these (from the weaker bases), lycodine (3) and des-N-methyl-a-obscurine (4), have been previously isolated and are of known structure but the other, obtained from countercurrent distribution of the stronger base fraction, is not previously described.The latter, base R, C16Hz4N202, forms only a monoperchlorate (B. HC104) and from infrared spectra its structure includes carbonyl and secondary amino groups. Acetylation of base R affords a neutral oily compound showing N-acetyl absorption in the infrared.Another new strong base containing only one nitrogen atom has also been found. Base L, which analyzes best for C18H31N04, is shown from its infrared spectrum to contain an 0-acetyl residue and two hydroxyl groups. Since the methiodide prepared from base L is normal (B. MeI) the nitrogen is-presumably tertiary and this is confirmed by acetylation which gives the diacetate CzoHaaNOe, identical with base 0 described elsewhere (1 (b)). Further acetylation of base 0 is ineffective so the other hydroxyl grouping was thought to be tertiary and this suspicion is strengthened by the chromium trioxide oxidation of base L to the hydroxy-keto-acetate, Ci~H29N04. The latter is readily hydrolyzed to the dihydroxy-ketone (desacetyldehydro-base L), C~~H Z~N O~, which shows infrared absorption attributable to a six-membered (or larger) ring ketone. Neither hydroxyl in desacetyldehydro-base L is suitably placed relative to the ketone for ready elimination.Base L hydrolyzes to a trihydroxy compound, desacetyl-base L, C16H29N03, which consumes no periodic acid implying that it contains no cis a-glycol system. Acetylation of desacetyl-base L a t room temperature gives rise to the diacetate, base 0 , but a t low temperature (5") a monoacetate is obtained which is not base L and must be the positional isomer, isobase L (cf. fawcettimine (5) and lycofoline (6)), since on further acetylation it also affords base 0. These preliminary results suggest that base L is a tricyclic tertiary base possessing a tertiary hydroxyl, a secondary equatorial hydroxyl, and a secondary axial 0-acetyl grouping.

Total Syntheses of Lycopodium Alkaloids (+)‐Fawcettimine, (+)‐Fawcettidine, and (−)‐8‐Deoxyserratinine

“…The Lycopodium alkaloids are a family of structurally complex natural products,1 which have provoked long‐term interests in their total syntheses because of their unique and fascinating architectures and potential biological activities 2. In particular, fawcettimine‐type Lycopodium alkaloids, such as fawcettimine ( 1 )3 and fawcettidine ( 2 )3, 4 (Scheme ), have attracted broad attention from the synthetic community in recent years, and a number of impressive total syntheses have been accomplished 5. Serratinine‐type Lycopodium alkaloids, such as 8‐deoxyserratinine ( 3 ),6 serratinine ( 4 ), serratine ( 5 ), and serratanidine ( 6 ), are structurally related to the fawcettimine‐type alkaloids, however, they possess a more complex molecular architecture with two vicinal quaternary stereogenic centers and a unique 6,5,6,5‐tetracyclic framework.…”

Applications of Mitsunobu Reaction in total synthesis of natural products

“…[263,264] (+)-Fawcettimine (228) belongs in Lycopodium class and contain a cis-fused [4.3.0] bicyclo structure and an azonane ring with a quaternary carbon. [265] (-)-8-Deoxyserratinine (227) also is a representative alkaloid in the same class. Its skeleton is built up via linking a nitrogen atom of the azonane ring with a C-4 carbon.…”

Fawcettimine‐Type Lycopodium Alkaloids as a Driving Force for Discoveries in Organic Synthesis

“…Fawcettidine ( 7 ) was first isolated from Lycopodium fawcetti by Burnell group in 1959 . It is not until 2008 that Dake group reported the first total synthesis of (+)− 7 .…”

“…From a biosynthetic point of view (Scheme ), derived from lysine and 3‐oxoglutaric acid, lycodoline ( 5 ) goes through a skeletal rearrangement to afford fawcettimine ( 6 ) . Further diversification of 6 delivers the majority members of the fawcettimine class, i. e., sieboldine ( 2 ), lycojapodine A ( 3 ), fawcettidine ( 7 ), lycoflexine ( 9 ), and etc.…”