Structure of homoplatensimide A: a potential key biosynthetic intermediate of platensimycin isolated from Streptomyces platensis

Platensimycin and platencin are novel natural product antibiotics that inhibit bacterial growth by inhibiting fatty acid biosynthesis enzymes FabF and FabF/FabH, respectively. Continued search for the natural congeners for structure activity relationship studies led to the isolation of a congener which possesses all of the twenty carbons of diterpenoid unit, a potential biosynthetic intermediate of platensic acid unit of platensimycin. Isolation, structure, and activity of homoplatensimide A and biosynthetic relationship to platensimycin have been described.     

Synthesis of gibberellins A8 and A56 from gibberellin A3

A mixture of gibberellin A₃ derivatives with 1(10)-ene-2,3-diol and 1(10)-ene-2,3-diol (2:5) groups, readily obtained from gibberellin A₃, has been used for a new and simple synthesis of gibberellin A₈ and its esters. The hydrolysis of GA₃ and the iodolactonization of a mixture of the 2-epimers was carried out in aqueous solution in a single flask, as also was a synthesis of GA₅₆ from GA₃ by a method that we have modified. The mixture of 1-iodides of GA₈ and GA₅₆ was separated by chromatography on SiO₂ in the form of methyl or p-bromophenacyl esters which were then deiodinated and the methyl or p-bromphenacyl ester of GA₈ was isolated. Free GA₈ was obtained by the dephenylation of the latter ester. By two-dimensional NMR spectroscopy we succeeded in assigning all the signals in the¹³C and¹H NMR spectra of the methyl esters of GA₈ and GA₅₆. In an attempt to obtain GA₅ methyl ester by the action of trimethylchlorosilane/sodium iodide on the 2,3-diol system in GA₅₆ methyl ester, the 8,13-epimer of the latter was formed, the structure of its molecule being established from the results of X-ray structural analysis.Novosibirsk Institute of Organic Chemistry, Siberian Division of the Russian Academy of Sciences. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 663–669, September–October, 1994.     

Uroleuconaphins A1 and B1, two red pigments from the aphid Uroleucon nigrotuberculatum (Olive)

Two novel red pigments, uroleuconaphins A₁ (1) and B₁ (2) were isolated from the aphid Uroleucon nigrotuberculatum (Olive). The structures and the absolute configurations of 1 and 2 were determined by single-crystal X-ray analysis of their derivatives. These structures were constituted as dimeric compounds of two molecules of quinone A (3), which were linked via a dihydrofuran ring system.     

Configuration interaction study of the oscillator strenghts for the A1--- A1 and A1--- A1 transitions of the water molecule

Oscillator strengths for transitions between the ¹A₁ ground state of water and its ¹A₁ and ¹A₁ excited states are computed employing two different theoretical approaches. In one series of calculations a common orthonormal one-electron basis is employed for all of the above states, while in the other type of treatment two different, mutually non-orthogonal, sets are used; the multireference single- and double-excitation (MRD CI) method is employed in each case, with configuration selection, to generate the various electronic wavefunctions. It is found that the use of ground-state SCF MOs leads to poor convergence in the wavefunctions of the (Rydberg-type) ¹A₁ and ¹A₁ excited states and consequently also for the corresponding --- and --- f-values; this behavior is seen to be closely related to the near degeneracy of the two excited states, each of which is a mixture of the 3a₁ → 3sa₁ and 1b₁ → 3pb₁ configurations. Analogous computations with the ¹B₁¹b₁ → 3sa₁ MOs show much better convergence properties, and the resulting f-values compare well with what is obtained when state-specific orbital sets are employed separately for ground and excited states and non-orthonormal techniques are applied to compute the desired transition moments. These results tend to confirm previous findings which indicate conceptual and computational advantages for the calculation of excited-state wavefunctions and properties within the context of a state-specific theory. They also show that although the goal of eliminating the dependence of MRD CI calculations on the choice of MO basis is very nearly approached for energy quantities, it is less satisfactorily achieved for other properties, especially when the existence of nearly degenerate electronic states is a critical factor.     

The 1B1, 1B2, 1A1, 1A2, 3A′(2B2), and 2A1 states of the 1,1-difluoromethane ion studied using multiconfiguration second-order perturbation theory

The 1²B₁(X²B₁), 1²B₂, 1²A₁, 1²A₂, 2²B₂, and 2²A₁ states of the ion were studied using CASPT2 and CASSCF methods. Calculations suggest that one should consider the 3²A′ state instead of 2²B₂. The CASPT2 T₀ calculations predict the energy ordering of 1²B₁(X²B₁), 1²B₂, 1²A₁, 1²A₂, 3²A′, and 2²A₁, which is in line with the experimental results by Pradeep and Shirley. The CASPT2 T₀ values for the 1²B₂, 1²A₂, 3²A′, and 2²A₁ states are close to the experimental values. The F-loss and H-loss dissociation processes were studied at the CASPT2//CASSCF level. The energy levels of low-lying states of are compared.     

Synthesis of coumermycin A1

A concise synthesis of the antibiotic coumermycin A₁, a natural product isolated from streptomyces, was achieved. In a key step, a selectively protected noviose sugar was prepared from novobiocin through a transglycosylation reaction with acetone.     

The reaction of gibberellins A1 and A7 with neutral manganese dioxide

Neutral manganese dioxide brings about oxidative lactonization and oxidative decarboxylation of gibberellins A₁ and A₇. The presence of a δ¹⁶-double bond is necessary for the occurrence of oxidative lactonization at C-15.     

Steroid glycosides of the roots ofCapsicum annuum. I. The structure of capsicosides A1, B1, and C1

Three new steroid glycosides of the spirostan series — capsicosides A₁, B₁, and C₁ — have been isolated from a methanolic extract of the roots of red pepper. In an investigation of the products of complete acid hydrolysis of these glycosides, a single aglycon — gitogenin — was identified. The complete chemical structure of each of the capsicosides has been shown with the aid of complete and partial acid hydrolysis, methylation and methanolysis, and periodate oxidation, and also by physicochemical methods of investigation.Institute of Chemistry, Academy of Sciences of the Moldavian SSR, Kishinev. Institute of Ecological Genetics, Academy of Sciences of the Moldavian SSR, Kishinev. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 708–712, November–December, 1986.     

Stereoselective syntheses of the glycosidase inhibitors hyacinthacine A2, hyacinthacine A3 and 5-epi-hyacinthacine A3

Stereoselective syntheses of the naturally occurring glycosidase inhibitors hyacinthacines A₂ and A₃ are reported. In the case of hyacinthacine A₂, the pyrrolizidine system was created from an acyclic precursor via a double cyclization procedure with a one-pot formation of two C-N bonds. In the case of hyacinthacine A₃, the two C-N bonds were created in separate steps. In addition, the non-natural epimer at C-5 of hyacinthacine A₃ was obtained.     

Toward carboxylate group functionalized A4, A2B2, A3B oxaporphyrins and zinc complex of oxaporphyrins

Series of new oxaporphyrins were isolated from the reaction of furan-1,4-diol, pyrrole, and an aldehyde under Lindsey’s conditions, which gives easy access to ester group functionalized oxaporphyrins. The ester substituents can be readily hydrolyzed to terminal carboxylic acid in the presence of KOH. The Zn(II) oxaporphyrins have been synthesized from the reaction of free base with ZnCl₂ and fully characterized by variable temperature NMR, 2D NMR, and single crystal X-ray diffraction studies.     

On the structure of thromboxane A2

The reactions of the 2-alkoxyoxetane 5 with sodium azide and methanol yield the α-azidoether 7 and the dimethyl acetal 8, respectively, paralleling reactions reported for TXA₂. The hydrolysis of 5 reported by Bruice to involve general acid catalysis proceeds at a rate similar to that reported for TXA₂. All these cleavage reactions are most likely to proceed by the same mechanism. These findings support structure 1 for TXA₂.     

Total synthesis of fluvirucinine A1

An efficient and highly stereocontrolled convergent synthesis of fluvirucinine A₁ is reported herein. In fluvirucinine A₁ both C₅-C₁₃ and C₁-C₄ fragments were accessed from a common intermediate 6 derived from (S)-Roche ester in 15 and 7 steps, respectively. The key steps involve Evans asymmetric alkylation, Sharpless asymmetric epoxidation, amidation and a ring-closing metathesis reaction (RCM) for macrocyclization.     

Synthesis of structure analogues of thromboxane A2

Analogues I of thromboxane A₂ (TXA₂) in which the ether linkages are replaced by carbon groupings have been synthesised by elaboration of a commercially available pinene derivative IIb.     

Discovery and antibacterial activity of lucensimycin C from Streptomyces lucensis

Protein synthesis is one of the key and validated antibacterial targets and its inhibition has led to the development of highly successful clinical drugs. Ribosomal protein S4 (RPSD) is a part of ribosomal machinery and a new potential target for antibacterial agents. Screening of microbial extracts using antisense sensitized rpsD strain in Staphylococcus aureus followed by chemical analysis led to the isolation of a new compound lucensimycin C, which is a key biosynthetic intermediate of the other lucensimycins. Isolation, structure elucidation, antibiotic activity, and biogenesis have been described.     

Total synthesis of natural (+)-hyacinthacine A6 and non-natural (+)-7a-epi-hyacinthacine A1 and (+)-5,7a-diepi-hyacinthacine A6

Naturally occurring (1S,2R,3R,5R,7aR)-1,2-dihydroxy-3-hydroxymethyl-5-methylpyrrolizidine [(+)-hyacinthacine A₆, 2] together with unnatural (1S,2R,3R,7aS)-1,2-dihydroxy-3-hydroxymethylpyrrolizidine [(+)-7a-epi-hyacinthacine A₁, 3] and (1S,2R,3R,5S,7aS)-1,2-dihydroxy-3-hydroxymethyl-5-methylpyrrolizidine [(+)-5,7a-diepi-hyacinthacine A₆, 4] have been synthesized from a DALDP derivative [5, (2R,3S,4R,5R)-3,4-dibenzyloxy-2′-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine], as the homochiral starting material. The synthetic process employed took advantages of Wittig methodology followed by internal lactamization, in the case of (+)-7a-epi-hyacinthacine A₁ (3), and reductive amination for (+)-hyacinthacine A₆ (2) and (+)-5,7a-diepi-hyacinthacine A₆ (4).     

Isolation and structure determination of a new thiopeptide globimycin from Streptomyces globisporus subsp. globisporus based on genome mining

Based on genome-mining, a new thiopeptide globimycin was discovered from the extract of Streptomyces globisporus subsp. globisporus, along with known one radamycin. The structure of globimycin was established by a combination of 2D NMR and ESI-MS experiments, and globimycin was identified to be a structural isomer of a known thiopeptide methylsulfomycin. The proposed biosynthetic gene cluster for globimycin and radamycin was found in the genome of S. globisporus subsp. globisporus.     

Isolation and structure of trichotomine and trichotomine G1

The new pigments, trichotomine (1) and trichotomine G₁ (12), which have a novel carbon skelton, have been isolated from the fruits of the plant Clerodendron trichotomum Thunb. On the basis of physical and chemical evidence, the structure of trichotomine (1)^1,2 was elucidated as an oxidative dimeric compound of 3 - oxo - 2,3 - 5,6 - tetrahydro - 11 H indolizino[8,7-b]indole 5-carboxylic acid and its stereostructure containing the absolute configuration was further determined by means of an x-ray crystallographic analysis.³ The structure of trichotomine G₁ (12), a N-β-D-glucopyranosyl trichotomine, is also based on spectral and chemical evidence. A N-β-D-glucopyranosyl indole derivative such as (12) is the first naturally occurring example.⁴