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.     

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.     

Total synthesis of calystegine A7

A straightforward chiral pool synthesis for the glycosidase inhibitor calystegine A₇ (isolated from Lycium chinense) from methyl α-d-glucopyranoside is described. Keysteps of this synthesis include a ultrasound assisted Zn-mediated tandem ring opening reaction followed by a Grubbs' catalyst mediated ring closure metathesis.     

Stereocontrolled synthesis of gibberellin A19 from gibberellic acid

The biosynthetically important C-20 gibberellin, gibberellin A₁₉5, has been prepared from the readily obtained C-19 gibberellin, gibberellic acid 8, by means of an efficient stereocontrolled ten step sequence.     

Total synthesis of BE-43547A2

An asymmetric total synthesis of BE-43547A₂ has been achieved in 16 steps (longest linear) on a 3.2 gram scale. The details of our efforts that led to the total synthesis of BE-43547A₂ were reported, the final 6 steps were optimized, and the overall yield was improved from 4.5% to 9.7%. The procedure utilized in the final 2 steps may serve as a better method for separating unstable APD compounds.     

Total synthesis of sorbistin A1 and a positional isomer

Total synthesis of sorbistin A₁ (1) and a positional isomer (7) is described for the first time in a regio- and stereo-controlled manner.     

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).     

Total synthesis of the (+)-antimycin A3 family: structure elucidation of (+)-antimycin A3a

(+)-Antimycin A_3a (AA_3a), one component of the natural antibiotic antimycin A₃, was synthesized using an asymmetric aza-Claisen rearrangement. The stereochemistry at the 2′ position on the acyloxy side chain of AA_3a was established as S-configuration by comparison of the synthetic AA_3a and the natural AA_3a.     

Total synthesis of carbomycin B and josamycin (leucomycin A3)

The stereospecific total synthesis of macrolide antibiotics, carbomycin B and josamycin (leucomycin A₃), is described. The key aglycone has been synthesized by coupling two segments of C1–C10 and C11–C16 portions, which are stereospecifically derived from glucose.     

The stereospecific synthesis of leukotriene A4 (LTA4), 5-epi-LTA4, 6-epi-LTA4 and 5-epi,6-epi-LTA4

The stereospecific syntheses of the four isomers of 6-formyl-5,6-epoxy hexanoic acid methyl ester $\text{8}$, $\text{15}$, $\text{23}$ and $\text{30}$ from Z-deoxy-D-ribose have allowed the preparation of methyl esters of LTA₄, $\text{1}$, and its three unnatural isomers.     

Synthesis of leukotrienes - new synthesis of natural leukotriene A4

The acetonides of D- or L-glyceraldehyde are chiral synthons for an efficient and versatile synthesis of the natural leukotrienes A₄, C₄, D₄, E₄ and equally can be used to prepare the corresponding unnatural analogues.     

A novel stereospecific synthesis of (±)-leukotriene A4(LTA4), methyl ester

The reaction of the phosphate $\text{1}$ with the expoxyaldehyde $\text{2}$ is reported as the key step in a novel stereospecific synthesis of (±)-LTA₄, methyl ester $\text{3}$.     

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.     

Total synthesis of bidensyneosides A2 and C: remarkable protecting group effects in glycosylation

Bidensyneosides are a group of five recently identified polyacetylenic glucosides from Bidens parviflora WILLD, a traditional Chinese medicinal plant that contains rich bioactive natural products. It was shown that bidensyneosides inhibited both histamine release and nitric oxide production. The synthesis of bidensyneoside A2 (2) and C (4) as well as 3-deoxybidensyneoside C (5) are described. These syntheses establish a synthetic entry to the bidensyneosides and confirm the stereochemistry at C3. Furthermore, a remarkable protecting group effect on orthoester formation was observed during the glycosylation reaction.     

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.     

Total synthesis of (+)-blastmycinone and formal synthesis of (+)-antimycin A3b

The formal synthesis of (+)-antimycin A_3b and the total synthesis of (+)-blastmycinone were achieved using, as a key step, a method developed by us for the synthesis of 2-methyl-1,3-diols via Ti(III)-mediated diastereo- and regioselective opening of trisubstituted 2,3-epoxy alcohols, to carry out the stereoselective construction of the hydroxy-acid segment. An interesting intramolecular radical translocation took place during the epoxide opening process transforming its vicinal PMB-ether in situ, into an ‘1,2-O-(p-methoxy)benzylidene’ ring.     

Total synthesis of topsentolide B2

A stereoselective total synthesis of topsentolide B₂, a selective cytotoxic oxylipin against SK-OV-3 and SK-MEL-2 cancer cell lines has been achieved based on asymmetric dihydroxylation, Roush allylation, and ring closing metathesis (RCM) reactions. The synthesis is completed in 11 steps and 2.1% overall yield.