Synthesis of (+)- and (−)-dihydropinidine by diastereoselective dimethylzinc promoted allylation of 2-methyltetrahydropyridine-N-oxide with an allylboronic ester

The enantiomers of the naturally occurring alkaloid dihydropinidine 1, potential antifeedants against the pine weevil, Hylobius abietis, were prepared by diastereoselective, dimethylzinc mediated addition of pinacolyl 2-propenylboronate 14 to nitrones (R)- and (S)-2-methyl tetrahydropyridine-N-oxide 3, prepared from d- and l-alanine, respectively.     

A concise synthesis of (±) and a total synthesis of (+)-epiquinamide

A total synthesis of the quinolizidine alkaloid (+)-epiquinamide 1 has been achieved starting from (−)-pipecolinic acid 3. The key step is the highly diastereoselective addition of a TBDMS-protected propargyl alcohol to a chiral aldehyde derived from 3 to give erythro alkynol 19, which is then easily transformed into the desired bicyclic skeleton.     

Isolation and structures of a new alkaloid alatamine and an insecticidal alkaloid wilfordine from euonymus alatus forma striatus (thunb.) makino.

A new alkaloid alatamine 5 and an insecticidal alkaloid wilfordine 6 were isolated together with evonine 2, neo-evonine 3, and euonymine4 from Euonymus alatus forma striatus (Thunb.) Makino (family Celastraceae). The structures of alatamine 5 and wilfordine 6 were fully established by chemical and spectroscopic methods. Transformation of alatamine 5 to wilfordine 6 was made.     

Heteroaromatic alkaloids,nakijinamines, from a sponge Suberites sp.

The structures of seven new secondary metabolites isolated from an Okinawan marine sponge Suberites sp., nakijinamines A (1), B (2), and F–I (3–6) and 6-bromoconicamin (7), have been elucidated on the basis of spectroscopic analysis, chemical conversion, and conformational analysis. These analyses disclosed that 1–6 were heteroaromatic alkaloids having the hybrid structures of an aaptamine-type alkaloid and an indole alkaloid, while 7 was a bromoindole alkaloid. Nakijinamine I (6) is the first example of an aaptamine-type alkaloid possessing a 1,4-dioxane ring. Antimicrobial activities of 1–7 were evaluated.     

Punicagranine,a new pyrrolizine alkaloid with anti-inflammatory activity from the peels of Punica granatum

A novel pyrrolizine alkaloid, 5-(furan-3-carbonyl)-2,3-dihydro-1H-pyrrolizine-7-carboxylic acid, was isolated from the peels of Punica granatum. Its structure was elucidated on the basis of 1D- and 2D-NMR and HR-ESI-MS spectra and then confirmed by X-ray diffraction. It represents a new type of natural pyrrolizine alkaloid, named, punicagranine (1). 1 showed inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. To our knowledge, the pyrrolizine alkaloid skeleton was reported in natural products for the first time.     

Studies on indian medicinal plants-XLIV: Solanoforthine,a new steroidal alkaloid from solanum seaforthianum. a note on the mass spectrum of solanocapsine

The structure of solanoforthine, m.p. 208–10°, [α]_D- 26.6°, a new steroidal alkaloid isolated from Solanum seaforthianum Andr., has been established as 3β-amino-22,26-epimino-16α,23-epoxy-22αH,25βH-cholest- 5- en -23β - ol 3, based on chemical and spectroscopic evidence and by its reduction to solanocapsine 2, another steroidal alkaloid encountered in the same species. The mass spectra of2 and 3 are discussed.     

Alkaloidosteroids from the starfish Lethasterias nanimensis chelifera

New ionic compounds containing an alkaloidal cation and a steroidal anion have been isolated by reverse-phase liquid chromatography from the extracts of the starfish Lethasterias nanimensis chelifera. Their structures have been elucidated by NMR and mass spectroscopy as 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolinium salts of 3-O-sulfoasterone 1, 3-O-sulfoisoasterone 2 and 3-O-sulfothornasterol A 3. In addition, the alkaloid 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA) 4 was found in this starfish.     

Anti-inflammatory chromone alkaloids and glycoside from Dysoxylum binectariferum

Herein we report isolation of a new chromone alkaloid chrotacumine K (12) from fruits and a chromone glycoside schumaniofioside A (13) from leaves of Dysoxylum binectariferum Hook f. Schumaniofioside A is reported for the first time from Meliaceae family. Other known alkaloids isolated include rohitukine (1) and chrotacumine E (6). The structure of new alkaloid 12 was elucidated on the basis of extensive 1D and 2D NMR analysis, synthesis and chemical hydrolysis. Chemically, chrotacumine K (12) is a 3′-O-acetyl rohitukine which on chemical or enzymatic hydrolysis produces rohitukine. The new alkaloid 12 is also present in seeds and stem-barks of this plant. The glycoside schumaniofioside A (13) is present only in leaves, and in abundance (～1% w/w of dried leaves). The isolated compounds and extracts were evaluated for in vitro effect on the proinflammatory cytokines (TNF-α and IL-6) in human monocytic THP-1 cells. The alkaloid 12 displayed potent inhibition (57%) of TNF-α at 0.3 µM, and was non-toxic to THP-1 cells up to 40 µM, indicating its excellent therapeutic window. Furthermore, a nitrobenzoyl ester analog 15e showed better inhibition of IL-6 than parent natural product chrotacumine K.     

BF3·Et2O catalyzed diastereoselective nucleophilic reactions of 3-silyloxypiperidine N,O-acetal with silyl enol ether and application to the asymmetric synthesis of (+)-febrifugine

The asymmetric BF₃·Et₂O catalyzed nucleophilic reactions of 3-silyloxypiperidine N,O-acetal 10 with silyl enol ethers derived from ketones are described. (+)-Febrifugine 1, an antimalarial alkaloid, was successfully synthesized based on this nucleophilic substitution. In addition, N,O-acetal 10 was synthesized from l-benzyl glutamate in 11 steps.     

Structural characterization of saturated pyrrolizidine alkaloids from Heliotropium transalpinum var. transalpinum Vell by NMR spectroscopy and theoretical calculations

The chemical investigation of Heliotropium transalpinum var. transalpinum Vell. (Boraginaceae) led to the isolation of transalpinecine (1), a novel pyrrolizidine alkaloid, in addition to known alkaloids subulacine (1β-2β-epoxy-1α-hydroxymethyl-8α-pyrrolizidine) (2), and 1α-2α-epoxy-1β-hydroxymethyl-8α-pyrrolizidine (3). The structures of the isolated compounds were elucidated based on spectroscopic data and theoretical calculations.     

Meloslines A and B,two novel indole alkaloids from Alstonia scholaris

An unprecedented indole alkaloid melosline A (1), with 6/5/6/6 tetracyclic ring skeleton, together with a new alkaloid melosline B (2) and one known compound (3) were isolated from the leaves and twigs of Alstonia scholaris. The new structures were elucidated by comprehensive spectroscopic analysis. The absolute configuration of compound 1 was confirmed by comparison of experimental data with calculated electronic circular dichroism (ECD). Compound 1 exhibited moderate cytotoxicity against MCF-7 cancer cell lines.     

Regio- and stereospecific models for the biosynthesis of the indole alkaloids—III : The Aspidosperma-Iboga-secodine relationship

In vitro transformation of the Aspidosperma alkaloid (?) tabersonine (1) to (±)-pseudocatharanthine (7) via (+) allocatharanthine (6) and dehydrosecodine A (3) is described as a model for the biochemical interconversion of Aspidosperma and Iboga alkaloids. Facile conversion of 1, 2 and 7 in xylene solution to the carbazole (9) suggests the intermediacy of dehydrosecodines (as 8) in these reactions. In methanol solution the racemic salt (12) is formed in 50% yield from catharanthine at 175°. Further pyrolysis of the salt yields the carbazole (9). Reduction of the salt (12) with NaBH₄ affords (±) dihydrosecodine (16) identical with the natural alkaloid from Rhazya stricta.     

Total synthesis of a dibromotyrosine alkaloid inhibitor of mycothiol S-conjugate amidase

Two complementary synthetic sequences are described for the first total synthesis of a dibromotyrosine alkaloid (1) reported to inhibit a critical mycobacterial enzyme, mycothiol S-conjugate amidase. The O-benzyloxime of 4-hydroxyphenylpyruvic acid was dibrominated and successively linked to a 3-aminopropyl chain, then to a 4-aminobutylguanidine unit, followed by selective deprotections to yield alkaloid 1. In an improved variant, the O-tetrahydropyranyloxime 12 was condensed with 4-aminobutylguanidine then dibrominated to phenol 14, which upon Mitsunobu coupling to a 3-aminopropyl segment and deprotection produced the target 1.     

Isolation,characterization, and NMR spectroscopic data of indole and oxindole alkaloids from Mitragyna speciosa

A new indole alkaloid, 7β-hydroxy-7H-mitraciliatine (1) and a new oxindole alkaloid, isospeciofoleine (2) together with nine known alkaloids were isolated from Mitragyna speciosa and characterized by NMR, CD, and MS spectroscopic data analyses. The ¹H and ¹³C NMR spectroscopic data of isospeciofoline (3), isorotundifoline (4), paynantheine (5), and 3-isopaynantheine (6) were also reported for the first time.     

Leucomidines A–C,novel alkaloids from Leuconotis griffithii

Two novel indole alkaloids and new quinazoline alkaloids, namely leucomidines A–C (1–3), were isolated from the barks of Leuconotis griffithii. The structures including the absolute configuration were elucidated on the basis of spectroscopic data, chemical means, and CD calculations. The quinazoline alkaloid, 3, is proposed to be derived from the same biogenetic precursor as the indole alkaloids 1 and 2.     

Three new dibromopyrrole alkaloids from the South China Sea sponge Agelas nemoechinata

Three new dibromopyrrole alkaloids, 9-N-methylcylindradine A (1), 1-N-methylugibohlin (2), nemoechine H (3), together with one known dibromopyrrole alkaloid N-methyldibromoisophakellin (4) were isolated from the South China Sea sponge Agelas nemoechinata. Their structures were elucidated by comprehensive spectroscopic methods including HRESIMS and NMR, and the absolute configuration of compound 1 was further confirmed by comparison of optical rotation. Compound 3 exhibited moderate cytotoxic activity against K562 and L-02 with IC₅₀ values of 6.1 μM and 12.3 μM, respectively.     

Lycocasuarines A–C,Lycopodium alkaloids from Lycopodiastrum casuarinoides

Three lycodine-type Lycopodium alkaloids (1–3) were isolated from Lycopodiastrum casuarinoides. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray crystallography, and computational methods. Compound 1 possesses a rearranged five-membered ring D resulting from C-8/C-15 cleavage and a new C-7/C-15 linkage. Compound 2 is the first Lycopodium alkaloid found to bear an additional carbon (C-17) directly bonded to C-8, which is particularly unusual from a biogenetic point of view. Compounds 1–3 were evaluated for acetylcholinesterase inhibitory activities.     

Isolation of a new indoxyl alkaloid,Amoenamide B,from Aspergillus amoenus NRRL 35600: Biosynthetic implications and correction of the structure of Speramide B

A new prenylated indoxyl alkaloid, Amoenamide B (1), was isolated from Aspergillus amoenus NRRL 35600 along with Asperochramide A (2). Although many prenylated oxindole alkaloids, containing bicyclo[2.2.2]diazaoctane cores, have been isolated from the fungus of the genera Aspergillus and Penicillium to date, 1 is the fourth compound with the indoxyl unit containing the cores. During the structure elucidation of 1, we found that the planar structure matched to that of Speramide A (3), isolated from A. ochraceus KM007, but the reported structure of 3 was incorrect and turned out to be that of Taichunamide H (4), recently isolated from A. versicolor HDN11-84.     

Nagelamides M and N, new bromopyrrole alkaloids from sponge Agelas species

Two new bromopyrrole alkaloids, nagelamides M (1) and N (2), have been isolated from an Okinawan marine sponge Agelas species, and the structures and stereochemistry were elucidated from the spectroscopic data. Nagelamide M (1) is a novel bromopyrrole alkaloid possessing a 2-amino-octahydropyrrolo[2,3-d]imidazole ring with a taurine unit, while nagelamide N (2) is a new bromopyrrole alkaloid possessing a 2-amino-tetrahydroimidazole-4-one ring with a taurine unit and 3-(dibromopyrrole-2-carboxamido)propanoic acid moiety. Nagelamides M (1) and N (2) exhibited antimicrobial activity.     

Zamamidine C, 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A, and 3,4-dihydromanzamine J N-oxide, new manzamine alkaloids from sponge Amphimedon sp.

New manzamine alkaloids, zamamidine C (1), 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A (2), and 3,4-dihydromanzamine J N-oxide (3), have been isolated from an Okinawan marine sponge Amphimedon species. The structures and stereochemistries of 1-3 were elucidated from the spectroscopic data and chemical derivatization. Zamamidine C (1) is a new manzamine alkaloid possessing a second β-carboline ring via an ethylene unit at N-2 of manzamine D, while 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A (2) is the first manzamine alkaloid possessing an epoxide ring at C-10 and C-11. Zamamidine C (1) showed significant antitrypanosomal activity against Trypanosoma brucei brucei, the parasite associated with sleeping sickness, and antimalarial activity against Plasmodium falciparum, the causative agent of malaria in vitro.