High-performance thin-layer chromatographic method for quantitative determination of 4alpha-methyl-24beta-ethyl-5alpha-cholesta-14,25-dien-3beta-ol, 24beta-ethylcholesta-5,9(11),22E-trien-3beta-ol, and betulinic acid in Clerodendrum inerme

A sensitive, selective, precise, and robust high-performance thin-layer chromatography method was developed and validated for analysis of two new recently isolated sterols, 4alpha-methyl-24beta-ethyl-5alpha-cholesta-14,25-dien-3beta-ol (1) and 24beta-ethylcholesta-5,9(11),22E-trien-3beta-ol (2), and a triterpene, betulinic acid (3), in Clerodendrum inerme extract. The method employed HPTLC plates precoated with silica gel 60F(254 )as the stationary phase. To achieve good separation, an optimised mobile phase consisting of toluene-acetone (94:06, v/v) was used (R(f )0.48, 0.34, and 0.22 for compounds 1, 2, and 3, respectively). Densitometric determination of the above compounds was carried out in reflection/absorption mode at 620 nm. Optimised chromatographic conditions provide well separated compact spots for the compounds 1, 2, and 3. The calibration curves were linear in the concentration range of 100-2500 ng/spot. The method was validated for precision, robustness, and recovery. The limits of detection and quantitation were 5, 6, and 10 microg/mL and 14, 18, and 29 microg/mL, respectively, for 1, 2, and 3. The method reported here is reproducible and convenient for quantitative analysis of these compounds in the aerial parts of C. inerme.     

17a-acetoxy-16,16-dimethyl-8-aza-D-homogona-1,3,5(10),9(11),13,17-hexaen-12-one, the product of acylotropic rearrangement at interaction of 16,16-dimethyl-8-aza-D-homogona-1,3,5(10),9(11),13-pentaene-12,17a-dione with acetic anthydride

On interaction of 16,16-dimethyl-8-aza-D-homogona-1,3,5(10),9(11),13-pentaene-12, 17a-dione with acetic anhydride acylotropic rearrangement occurs with the formation of a single product, viz. 17a-acetoxy-16, 16-dimethyl-8-aza-D-homogona-1,3,5(10),9(11),-13, 17a-hexaen-12-one. The effect of sodium acetate and of acetic acid concentration on the result of the reaction has been studied. The structure of the product was confirmed by data of elemental analysis, IR, UV,¹H, and¹³C NMR spectroscopy, mass spectrometry, and also X-ray structural analysis. Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk 220141. Scientific Research Institute of Physicochemical Problems, Belarussian State University, Minsk 220080. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1376–1387, October, 1999.     

A new synthesis of a potent cancer chemopreventive agent, 13-oxo-15,16-dinorlabda-8(17),11E-dien-19-oic acid from trans-communic acid

The first synthesis of a labdane diterpenoid, (-)-13-oxo-15,16-dinorlabda-8(17),11E-dien-19-oic acid [(-)-1a], isolated from the stem bark of Thuja standishii (GORD.) CARR., from the major component trans-communic acid (3a) is described.     

The first enantioselective synthesis of the amino acid, (2S,3S,4R)-gamma-hydroxyisoleucine using a palladium(II) catalysed 3,3-sigmatropic rearrangement

A synthetic route towards the synthesis of (2S,3S,4R)-gamma-hydroxyisoleucine, the amino acid component of the natural product, funebrine has been developed using as the key step, a palladium(II) catalysed 3,3-sigmatropic rearrangement to create the (2S)-stereogenic centre.     

Kottamide E, the first example of a natural product bearing the amino acid 4-amino-1,2-dithiolane-4-carboxylic acid (Adt)

Kottamide E, a novel alkaloid containing dibrominated indole enamide, oxalic acid diamide and 4-amino-1,2-dithiolane-4-carboxamide moieties, has been isolated from the New Zealand ascidian Pycnoclavella kottae. Characterisation was achieved by interpretation of spectroscopic data.     

Amino acids derivatives that stabilize secondary structures of polypeptides-- : I. Synthesis of LL-3-amino-2-piperidone-6-carboxylic acid (LL-Acp), a novel beta-turn-forming amino acid

A six-step synthesis is reported of $\text{LL}$-3-amino-2-piperidone-6-carboxylic acid from $\text{L}$-homoserine lactone and the $\text{mono}$-$\text{t}$-butyl ester on $\text{N}$-benzyloxycarbonylaminomalonic acid. Evidence of chiral integrity is discussed.     

Glycosylation of triterpenoids of the dammarane series. IX. β-D-glucopyranosides of 20(S),24(R)-epoxydammarane-3α,12β,17α,25-tetraol 25-tetraol

Glycosides have been synthesized from 20(S),24(R)-epoxy-dammarane-3α,12β,17α, 25-tetraol, which was isolated from the leaves ofBetula costata. Exhaustive glycosylation of betulafolienetetraol oxide with α-acetobromoglucose in the presence of mercury cyanide gave an acetylated 3,12,25-triglucoside (yield 61%), while glycosylation in the presence of insoluble silver compounds led to the formation of 3- and 12-mono- and 3,12- and 12,25-diglucopyranosides (total yield 57–82%). The structures of the glucosides obtained have been established on the basis of the results of IR and¹H and¹³C NMR spectroscopy.     

Synthesis of the nonproteinogenic amino acid (2S,3S,4S)-3-hydroxy-4-methylproline,a constituent of echinocandins

An enantioselective synthesis of the unusual 3,4-disubstituted proline 2, a constituent of antifungal echinocandins, has been achieved through 1,3-dipolar cycloaddition of N-methylnitrone to the α,β-unsaturated lactam 4 derived from (S)-pyroglutaminol.     

A general strategy for the synthesis of cladiellin diterpenes: enantioselective total syntheses of 6-acetoxycladiell-7(16),11-dien-3-ol (deacetoxyalcyonin acetate), cladiell-11-ene-3,6,7-triol, sclerophytin A, and the initially purported structure of sclerophytin A

Enantioselective total syntheses of the cladiellin diterpenes, 6-acetoxycladiell-7(16),11-dien-3-ol (deacetoxyalcyonin acetate, 6), cladiell-11-ene-3,6,7-triol (1), sclerophytin A (8), and tetracyclic diether 7, have been achieved by differential elaboration of tricyclic allylic alcohol 57. The central step in these syntheses is acid-promoted condensation of alpha,beta-unsaturated aldehydes 45, 69 or 87, and cyclohexadienyl diol 44 to form, with complete stereocontrol, the hexahydroisobenzofuran core and five stereocenters of these cladiellin diterpenes. These syntheses also feature stereospecific photolytic deformylation of beta,gamma-unsaturated aldehydes 46, 70, and 71 to remove the extraneous carbon introduced in the Prins-pinacol step; chemo- and stereoselective hydroxyl-directed epoxidation of 49, 72, and 90 followed by regioselective reductive opening with hydride to install the C3 tertiary hydroxyl group; and a diastereoselective Nozaki-Hiyama-Kishi cyclization of iodoaldehyde 56 to forge the oxacyclononane ring and the C6 hydroxyl stereocenter. Other key transformations include chemo- and stereoselective hydroxyl-directed epoxidation of tricyclic allylic alcohol 57 followed by regioselective reductive opening with hydride to install the C7 tertiary hydroxyl center of 1 and 8; chemo-, regio-, and stereoselective intramolecular oxymercuration-reductive demercuration of dienyl diol 62 to form the bridging tetrahydropyran ring of tetracyclic diether 7; and photochemical isomerization of the endocyclic double bond of 92 and 1 to give exocyclic congeners 7 and 8. The absolute stereochemistry of the synthetic products originates from two chiral nonracemic starting materials, (S)-(+)-carvone and (S)-(-)-glycidol. These syntheses define a versatile and concise strategy for the total synthesis of cladiellin diterpenes and provide additional illustrations of the uncommon utility of pinacol-terminated cationic cyclizations for the stereocontrolled synthesis of complex oxacyclic products.     

Total synthesis and absolute configuration of liverwort diterpenes, (-)-13(15)E,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene and (-)-13(15)Z,16E-3beta,4beta-Epoxy-18-hydroxysphenoloba-13(15),16-diene,by use of the ring closing metathesis reaction applied to seven-membered carbocycles with a trisubstituted double bond

Seven-membered cyclic compounds possessing trisubstituted double bonds have been effectively constructed employing the Grubbs catalyst to effect olefin metathesis. The keto ester does not undergo cyclization; however, alcohols protected by the silyl groups smoothly cyclized into seven-membered compounds. The product was successfully converted to (-)-13(15)E,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene and (-)-13(15)Z,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene, liverwort diterpenes isolated from Anastrophyllum auritum to establish the absolute configuration.     

Stereoselective synthesis of protected (2R,3R,4S)-4,7-diamino-2,3-dihydroxyheptanoic acid: a novel amino acid of callipeltins A and D

An orthogonally protected derivative 1 of (2R,3R,4S)-4,7-diamino-2,3-dihydroxyheptanoic acid, the unusual amino acid residue of the biologically active marine peptides such as callipeltins A and D and neamphamide A, was efficiently prepared in 10 steps and 30% overall yield from a commercially available L-ornithine derivative 2. The key step includes the N-diphenylmethylene-controlled diastereoselective dihydroxylation of (Z)-ester 3 with >13:1 selectivity for the desired isomer.     

Application of the gold(I)-Catalyzed aldol reaction to a stereoselective synthesis of (2S, 3R, 4R, 6E)-3-Hydroxy-4-methyl-2-(methylamino)oct-6-enoic Acid ( = MeBmt), Cyclosporin's unusual amino acid

The title compound 8 was prepared in three steps starting from the optically pure aldehyde (2R, 4E)-2-methyl-hex-4-enal ( 3 ), thus constituting the shortest synthetic approach reported. Two of the three stereogenic centers in the product were generated in a coupling reaction of 3 with ethyl isocyanoacetate, catalyzed by a gold(I)/chiral ferrocenylphosphine system, giving the dihydrooxazole 5 in 85% diastereoselectivity (mismatchedcase). The weak effect of double stereodifferentiation in this reaction (matched case 90% ds) is discussed. N-Methylation and hydrolytic ring opening of 5 gave the protected form 7 of MeBmt, The X-ray diffraction study carried out on 7 confirms the absolute configuration of the two stereogenic centers formed in the gold(I)-catalytic reaction.