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.     

Total synthesis of the marine alkaloid halitulin

The structure of the strongly cytotoxic marine alkaloid halitulin (1) has been confirmed by total synthesis and its absolute configuration determined as (15S). The synthesis follows a strategy previously reported by one of us and uses an efficient preparation of the quinoline-7,8-diol unit by modified Baeyer-Villiger and Skraup reactions. The O-benzyl protecting groups were removed in the last step of the synthesis by transfer hydrogenolysis without concomitant reduction of the quinoline ring. The method can be applied for the synthesis of halitulin analogues.     

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.     

Alkaloids ofBuxus balearica. I

Conclusions Seven alkaloids have been isolated from the leaves ofBuxus balearica Lam: alkaloid A (apparently identical with baleabuxine), C₃₀H₅₀N₂O₂; alkaloid B (possibly N-isobutyrylbaleabuxidienine F), C₃₀H₅₀N₂O₃; alkaloid C (new), C₂₆H₄₁NO, with a C=C-C=O grouping and a N(CH₃)₂ group; alkaloid D, C₃₀H₅₀N₂O₄; alkaloid E (new), C₂₇H₅₀N₂O₃; alkaloid F (possibly identical with cyclomicrophylline B), C₂₇H₄₆N₂O₂; and alkaloid G (new), C₂₇H₄₆N₂O₃.Khimiya Prirodnykh Soedinenii, Vol. 5, No. 1, pp. 26–28, 1969     

A new class of indole alkaloid ‘elegansamine’ constructed from a monoterpenoid indole alkaloid and an iridoid

Elegansamine (1) isolated from Gelsemium elegans (Thailand) was proved to be a new type of alkaloid composed by the carbon-carbon linkage of a monoterpenoid indole alkaloid and a monoterpene unit having the iridoid skeleton.     

Synthese d'oligosaccharides sur polymere support—IV : Reactions sur polymere “popcorn”

The different steps leading to oligosaccharide synthesis on polymeric support have been studied in the case of a functionalized ”popcorn” polystyrene: anchoring of the first glucidic group, unblocking of a selectively protected hydroxyl group, glycosylation and cleavage of the glucide support bond. The first glucidic unit is attached by a benzoic ester bond cleaved by methanolysis (Zemplén's method); β-benzoylpropionic ester was used as temporary protecting group. The synthesis of benzyl - 2 - acetamido - 4,6 - di - O - acetyl - 3 - O - (2 - acetamido - 3,4,6 - tri - O - acetyl - 2 - deoxy - β - D - glucopyranosyl) - 2 - deoxy - α - D - glucopyranoside is described as an example.     

Kororamide A,a new tribrominated indole alkaloid from the Australian bryozoan Amathia tortuosa

A new tribrominated indole alkaloid, kororamide A together with the known alkaloid convolutamine F, were isolated through the application of mass directed purification from the bryozoan, Amathia tortuosa collected from northern New South Wales, Australia. The structure of kororamide A was deduced from the analysis of 1D/2D NMR and MS data. Kororamide A exists in solution as a mixture of interconverting cis–trans amide regioisomers in a ratio of 4:5. Bioactivity testing demonstrated that kororamide A was marginally active against chloroquine-sensitive and resistant strains of the malarial parasite Plasmodium falciparum, and was inactive against normal human cell lines.     

A new phenanthroindolizidine alkaloid from Tylophora indica

A new phenanthroindolizidine alkaloid, 3-O-demethyl tylophorinidine (VI), was isolated from the aerial (leaves and stem) parts of Tylophora indica and characterized using different spectral techniques. Gel chromatography and reverse phase preparative HPLC were used for sample purification. The new alkaloid, VI, was screened for anticancer activity against a panel of different cancer cell lines and it showed significant anticancer activity with IC₅₀ value in the range of 0.89?C1.40 ??M.     

One-pot N-dealkylation and acid-catalyzed rearrangement of morphinans into aporphines

The one-pot N-demethylation and acid-catalyzed rearrangement of morphinan-N-oxides offers a new, shorter and more efficient route to neuropharmacologically important N-substituted aporphines. An improved procedure is described for the preparation of the starting alkaloid N-oxides using Na₂WO₄ as catalyst. The transetherification during the rearrangement of codeinone into 2-O-alkyl-norapocodeines is documented.     

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.     

A synthesis of 5-hydroxysedamine using hydroformylation

A synthesis of 5-hydroxysedamine, a Sedum alkaloid, has been completed using N,O-heterocycle chemistry to establish the aminoalcohol structure, hydroformylation to form the piperidine ring and diastereoselective dihydroxylation to introduce the 5-hydroxy group.     

Three New C19‐Diterpenoid Alkaloids from Aconitum forrestii

A further study of the alkaloid constituents of Aconitum forrestii led to the isolation of three new C₁₉‐diterpenoid alkaloids, named 14‐acetoxy‐8‐O‐methylsachaconitine ( 1 ), 14‐acetoxyscaconine ( 2 ), and 8‐O‐ethylcammaconine ( 3 ). Their structures were determined by UV, IR, and MS, 1D‐ and 2D‐NMR analyses.     

Synthesis of pyrrolidin-3-ones from dihydropyran precursors via spiro-N,O-acetals

2,2-Disubstituted pyrrolidin-3-ones are prepared in three steps from simple dihydropyran derivatives; the key spiro-N,O-acetal intermediate is a useful N-sulfonylketoiminium ion precursor. This route represents a formal synthesis of the indolizidine alkaloid core, with potential application to pyrrolizidines and quinolizidines.     

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.     

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.     

Crystal structures and polymorphism in compounds Bi6+xT1−xP2O15+y, T=first row transition metals and Pb

The compounds Bi_6+xT_1−xP₂O_15+y, T=Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn and Pb display five polymorphic forms. Polymorph A is formed by the Ti, Mn, Fe and Ni phases. Polymorph B is exhibited by Co and Cu compounds. The Cr phase crystallizes as polymorphic form C and the Zn phase crystallizes as polymorph D. The Pb compound crystallizes in a new structure type designated as polymorph E. The transition metal crystal structures demonstrate a similar motive. OBi₄ tetrahedra share edges to form two-dimensional Bi₂O₂ layers that are spanned by PO₄ tetrahedra and TO_6−y octahedra, pyramids and a trigonal bipyramid to form a three-dimensional network. Polymorph A crystallizes in space group C2; polymorph B is centrosymmetric with space group C2/c, the unit cell parameters differ and the unit cell volume is about double. Polymorph C crystallizes in space group and polymorph D exhibits space group C2. Bi_6.4Pb_0.6P₂O_15.2 can be considered as polymorph E, space group C2, with a new crystal structure but related stoichiometry.     

Thalicfoetine,a novel isoquinoline alkaloid with antibacterial activity from Thalictrum foetidum

Thalicfoetine (1), the first O-bridged spirobenzylisoquinoline alkaloid possesses a spiro tetrahydropyridine-furanone core, was isolated from the roots of Thalictrum foetidum. Its structure was elucidated by extensive spectroscopic analyses and ECD calculation. Moreover, 1 exhibited antibacterial activity against Bacillus subtilis significantly with MIC value of 3.12 μg/mL.     

Two novel indole alkaloids, Kopsiyunnanines A and B, from a Yunnan Kopsia

Two novel indole alkaloids having unusual skeletons were isolated from the aerial part of Yunnan Kopsia arborea. Kopsiyunnanine A (1) is a new class of bisindole alkaloid composed of vallesiachotamine (modified Corynanthe-type) and Aspidospermatan-type alkaloids. Kopsiyunnanine B (2) is a new Corynanthe-type oxindole alkaloid rearranged by D ring rotation.     

Tomato steroidal alkaloid glycosides, esculeosides A and B, from ripe fruits

Major novel steroidal alkaloid glycosides, named esculeoside A (1) and esculeoside B (2), have been isolated from the pink color-type and the red color-type, respectively, of the ripe tomato fruits of Lycopersicon esculentum MILL. for the first time. The structures of 1 and 2 have been characterized as 3-O-β-lycotetraosyl (5S,22S,23S,25S)-23-acetoxy-3β,27-dihydroxyspirosolane 27-O-β-d-glucopyranoside and 3-O-β-lycotetraosyl (5S,22S,23R,25S)-22,26-epimino-16β,23-epoxy-3β,23,27-trihydroxycholestane 27-O-β-d-glucopyranoside, respectively.     

Geissospermiculatine,a New Alkaloid from Geissospermum reticulatum Bark

A new alkaloid, geissospermiculatine was characterized in Geissospermum reticulatum A. H. Gentry bark (Apocynaceae). Here, following a simplified isolation protocol, the structure of the alkaloid was elucidated through GC-MS, LC-MS/MS, 1D, and 2D NMR (COSY, ROESY, HSQC, HMBC, ¹H-¹⁵N HMBC). Cytotoxic properties were evaluated in vitro on malignant THP-1 cells, and the results demonstrated that the cytotoxicity of the alkaloid (30  μg/mL) was comparable with staurosporine (10  μM). Additionally, the toxicity was tested on zebrafish (Danio rerio) embryos in vivo by monitoring their development (0–72 h); toxicity was not evident at 30  μg/mL.