Efficient total synthesis of manzacidin B

The highly diastereoselective synthesis of the marine natural product, (?)-manzacidin B, is described. A novel copper-catalyzed aldol reaction of the α-methylserine-derived aldehyde with an isocyanoacetate possessing (1R)-camphorsultam as the chiral auxiliary proceeded in a highly diastereoselective manner to give the (4R,5R,6R)-adduct, which was converted into manzacidin B in a few steps.     

Practical syntheses of proposed and revised manzacidin B and their congeners

A concise and highly stereoselective total synthesis of manzacidin B and its congeners has been developed following chelation-controlled syn-epoxidation and Lewis acid catalyzed intramolecular regioselective epoxide ring opening to generate the quarternary amine center. Elaboration of the triol moiety to the target molecule was achieved in good overall yield, representing practical total syntheses of manzacidin B and its congeners. From the XRD, NMR, and analytical data, the correct structure of natural manzacidin B, (4R,5R,6R)-6, was confirmed.     

Determination of the absolute structure of (+)-cystothiazole B

Palladium-catalyzed cyclization-methoxycarbonylation of (2R,3S)-3-methylpenta-4-yne-1,2-diol (6) derived from (2R,3S)-epoxy butanoate 5, followed by methylation, gave the tetrahydro-2-furylidene acetate (-)-7, which was converted to the left-half aldehyde (+)-3. A Wittig reaction between (+)-3 and the phosphoranylide derived from the bithiazole-type phosphonium iodide 4 using lithium bis(trimethylsilyl)amide afforded (+)-cystothiazole B (2), the spectral data of which were identical to those of the natural product (+)-2. Thus the stereochemistry of cystothiazole B (2) was confirmed to be [4R, 5S, 6(E)].     

Synthesis of optically active petiodial and determination of its absolute structure

(+)-Petiodial was synthesized starting from (+)-genipin in nine steps via alkylation at C-11 of genipin and isomerization of the double bond in the cyclopentene ring as crucial points. The absolute structure of petiodial was determined by this synthesis.     

Synthesis of marine sponge alkaloid hachijodine B and a comment on the structure of ikimine B and on the absolute configuration of niphatesine D

The syntheses of the proposed structures of hachijodine B 1, ikimine B 2 and niphatesine D 3 from S-citronellol are described. Our results suggest that the gross structures of hachijodine B and niphatesine D are correct, but that ikimine B was incorrectly assigned. We have also established that the previous absolute stereochemical assignment for niphatesine D is unreliable.     

Synthesis of manzacidin A and C: efficient construction of quaternary carbon stereocenters bearing nitrogen substituents

An efficient synthetic method for stereoselective construction of asymmetric quaternary carbon stereocenters, bearing nitrogen in the form of Boc-protected allyl amines, has been developed. This methodology is employed in the synthesis of marine alkaloids, manzacidin A and C.     

Synthesis and absolute stereochemistry of roseophilin

The enantiospecific total synthesis of natural roseophilin has been completed in 7.0% overall yield over 15 steps by means of an asymmetric cyclopentannelation. This establishes the absolute configuration of the natural product as 22R,23R. Cyclopentenone (+)-12 was prepared in 78% yield and 86% ee in the key step.     

Synthesis,structure revision,and absolute configuration of (+)-didemniserinolipid B,a serinol marine natural product from a tunicate Didemnum sp

[structure: see text] En route to proving the absolute and relative stereochemistry, through synthesis, of (+)-didemniserinolipid B (1), the first natural serinolipid isolated from a tunicate Didemnum sp., it was discovered that the isolated natural product was in fact the 31-sulfate configured 8R,9R,10R,13S,30S. This structural reassignment was only possible after the development of a microwave-assisted method for the sulfation of unreactive hydroxyl groups.     

An efficient asymmetric synthesis of manzacidin C

A brief synthesis of manzacidin C based on a chiral silane-promoted diastereo- and enatioselective acylhydrazone-alkene [3 + 2] cycloaddition reaction has been achieved. This synthesis is the first synthesis of any of the manzacidins wherein the C(4) and C(6) stereocenters are established in a single highly stereoselective step.     

The structure and absolute configuration of heterophylloidine

The structure and absolute configuration of heterophylloidine, a new C₂₀-diterpenoid alkaloid isolated from $\text{Aconitum heterophylloides}$ Stapf, have been determined with the aid of ¹³C NMR spectral data and single-crystall X-ray analysis of the product obtained by treatment of heterophylloidine with aqueous hydrobromic acid.     

Enantioselective total syntheses of nankakurines A and B: confirmation of structure and establishment of absolute configuration

Total syntheses of (+)-nankakurine A (2) and (+)-nankakurine B (3) were accomplished by a sequence that employs an intramolecular dipolar cycloaddition of an azomethine imine intermediate to form the azatricyclic moiety and establish the relative configuration of the spiropiperidine ring. These syntheses, together with the synthesis of the originally purported structure 1 of nankakurine A, rigorously establish the relative and absolute configuration of these structurally unusual Lycopodium alkaloids. The syntheses are sufficiently concise that gram quantities of (+)-nankakurine A (2) and (+)-nankakurine B (3) will be available for further biological studies.     

Synthesis and absolute configuration of annuionone A

Synthesis of both enantiomers of annuionone A (1), an allelopathic agent isolated from Helianthus annuus (sunflower), was accomplished. The absolute configuration of the naturally occurring 1 was determined to be 1S,5R,8R.     

Synthesis and absolute configuration of substituted morpholines

We studied methods of stereospecific synthesis that enabled us to obtain variously substituted morpholinic compounds and to determine their absolute configuration. From a study of the chiroptical properties of synthetic N-[2-pyridyl-N-oxide] derivatives of optically active morpholines, it was possible to correlate the sign of the Cotton effect with the absolute configuration. This correlation agrees with that previously established for derivatives of the piperidine type. By evaluating the various contributions to the Cotton effect of substituents in positions 2 and 3, we established the absolute configuration of bicyclic compounds condensed in the two positions mentioned above.     

Synthesis,crystal structure,and absolute configuration of the enantiomers of chiral drug xibenolol hydrochloride

Based on the features of its crystallization, racemic 3-(2,3-dimethylphenoxy)propane-1,2-diol 2, the synthetic precursor of the chiral drug xibenolol 1, was resolved into pure enantiomers by the direct method of entrainment. The enantiomers of diol 2 through a Mitsunobu reaction were converted into the nonracemic 1,2-epoxy-3-(2,3-dimethylphenoxy)propanes (S)- and (R)-3, and then into the xibenolol enantiomers. Single crystals of (+)- and (?)-1·HCl were studied by X-ray diffraction. On the basis of the Flack parameter, the absolute (R)- and (S)-configurations were assigned to these compounds and to the other intermediate chiral substances.     

The absolute molecular structure of Hodgkinsine

Preliminary crystallographic analysis of crystals of the respective benzene and bromobenzene adducts of hodgkinsine, an alkaloid from Hodgkinsonia frutescens F. Muell. (family Rubiaceae), together with mass spectral evidence suggested a formulation for hodgkinsine based on three N-methyltryptamine units. X-ray analysis of crystals of the trimethiodide monohydrate, C₃₃H₃₈N₆.3CH₃I.H₂O, has defined the absolute molecular structure of hodgkinsine. These crystals are monoclinic belonging to the space group P2₁, with a = 12·779, b = 13·923, c = 11·190 Å, β = 107·78°, Z = 2. The crystal structure has been solved from data collected with CuKα radiation on a single-crystal diffractometer and refined by least-squares procedures from intensity data re-collected with MoKα radiation. The absolute chirality was defined by Bijvoet's technique. The molecular structure of hodgkinsine is given as I. Two of the N-methyltryptamine units T″ and T″' are in the same configuration while T′ is in the opposite. The CD spectrum of hodgkinsine is discussed in relation to these units of different chiralities.     

Total synthesis and absolute configuration of nocardioazine B

The first total synthesis of the indole alkaloid nocardioazine B was accomplished in 10 steps with an overall yield of 11.8%, establishing the absolute stereochemistry of the natural product.     

Molecular structure and absolute configuration of α-chloromercurycamphene

Conclusions The methods of x-ray structural analysis have been used to determine the crystal and molecular structures and the absolute conformation of -chloromercurycamphene.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2021–2026, September, 1979.