The structure and absolute configuration of the antibiotic aphidicolin: a tetracyclic diterpenoid containing a new ring system

1973 ◽  
pp. 2841 ◽  
Author(s):  
William Dalziel ◽  
Barrie Hesp ◽  
Karen M. Stevenson ◽  
John A. J. Jarvis
Keyword(s):  
Absolute Configuration ◽  
Ring System

Cytochalasan Alkaloids as TRAIL Sensitizers from an Endophytic Fungus Chaetomium sp.

Planta Medica ◽  
2021 ◽  
Author(s):  
Hanli Ruan ◽  
Ying Gao ◽  
Ruihua Mao ◽  
Ye Liu ◽  
Ming Zhou
Keyword(s):  
Colorectal Cancer ◽  
Absolute Configuration ◽  
Endophytic Fungus ◽  
Cancer Cell Line ◽  
Ring System ◽  
Ht29 Cell ◽  
Colorectal Cancer Cell Line ◽  
X Ray ◽  
Fibrous Roots ◽  
Trail Sensitivity

Two new cytochalasans with a rare 6/6/5/5/7 pentacyclic ring system, named chaetoconvosins C−D (1−2), together with two known congeners (3−4), were isolated from the fermentation of an endophytic fungus, Chaetomium sp. SG-01, harbored in the fibrous roots of Schisandra glaucescens Diels. Their structures including the absolute configuration were elucidated by extensive spectroscopic (HRESIMS, NMR, and ECD) and X-ray crystallographic analyses. The TRAIL sensitivity of 1–4 in a TRAIL-resistant HT29 colorectal cancer cell line was evaluated, which revealed that co-treatment of 1–4 at 50 µM with TRAIL (150 ng/mL) reduced the HT29 cell viability by 19.0%, 24.1%, 17.9%, and 15.5%, respectively, compared to treatment with 1–4 alone.

The Boger Synthesis of (-)-Vindoline

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Absolute Configuration ◽  
Secondary Alcohol ◽  
Ring System ◽  
Simple Solution ◽  
Relative Configuration ◽  
Amine Oxidation ◽  
Formidable Challenge ◽  
Starting Point ◽  
La Jolla ◽  
Stereogenic Center

The periwinkle-derived alkaloids vinblastine 2a and vincristine 2b are still mainstays of cancer chemotherapy. The more complex half of these dimeric alkaloids, vindoline 1, presents a formidable challenge for total synthesis. Building on his previous work (Organic Lett. 2005, 7, 4539), Dale L. Boger of Scripps/La Jolla devised (J. Am. Chem. Soc. 2010, 132, 3685) a strikingly simple solution to this problem based on sequential cycloaddition. The starting point for the synthesis was the ester 3, derived from D-asparagine. This was extended to 4, condensation of which with 5 gave the enol ether 6. On heating, 7 cyclized to 8, which lost N2 to give the zwitterion 9. Addition of the intermediate 9 to the indole then gave 10. In one reaction, the entire ring system of vindoline, appropriately oxygenated, was assembled, with the original stereogenic center from D-asparagine directing the relative and absolute configuration of the final product. To complete the synthesis, the pendant carbon on 11 had to be incorporated into the pentacyclic skeleton. After adjusting the relative configuration of the secondary alcohol, the N was rendered nucleophilic by reduction of the amide to the amine. Oxidation delivered 14, which on activation as the tosylate smoothly rearranged to the ketone 15. Reduction and regioselective dehydration then completed the synthesis of vindoline 1.

The Kozmin Synthesis of Spirofungin A

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Absolute Configuration ◽  
Journal Article ◽  
Ring System ◽  
Spatial Proximity ◽  
Silyl Ether ◽  
Secondary Alcohols ◽  
Ring Closing Metathesis ◽  
Cross Metathesis ◽  
The University ◽  
Flexible Ring

Often, 6,6-spiroketals such as Spirofungin A 3 have a strong anomeric bias. Spirofungin A does not, as the epimer favored by double anomeric stabilization suffers from destabilizing steric interactions. In his synthesis of 3, Sergey A. Kozmin of the University of Chicago took advantage (Angew. Chem. Int. Ed. 2007, 46, 8854) of the normally-destablizing spatial proximity of the two alkyl branches of 3, joining them with a siloxy linker to assure the anomeric preference of the spiroketal. The assembly of 1 showcased the power of asymmetric crotylation, and of Professor Kozmin’s linchpin cyclopropenone ketal cross metathesis. To achieve the syn relative (and absolute) configuration of 6, commercial cis-2-butene was metalated, then condensed with the Brown (+)-MeOB(Ipc)2 auxiliary. The accompanying Supporting Information, accessible via the online HTML version of the journal article, includes a succinct but detailed procedure for carrying out this homologation. For the anti relative (and absolute) configuration of 9, it is more convenient to use the tartrate 8 introduced by Roush. Driven by the release of the ring strain inherent in 10, ring opening cross metathesis with 6 proceeded to give the 1:1 adduct 11 in near quantitative yield. The derived cross-linked silyl ether 12 underwent smooth ring-closing metathesis to the dienone 1. On hydogenation, the now-flexible ring system could fold into the spiro ketal. With the primary and secondary alcohols bridged by the linking silyl ether, only one anomeric form, 2, of the spiro ketal was energetically accessible. A remaining challenge was the stereocontrolled construction of the trisubstituted alkene. To this end, the aldehyde 13 was homologated to the dibromide 14. Pd-mediated coupling of the alkenyl stannane 15 with 14 was selective for the E bromide. The residual Z bromide was then coupled with Zn(CH3)2 to give 16. These steps, and the final steps to complete the construction of spirofungin A 3 , could be carried out without exposure to equilibrating acid, so the carefully established spiro ketal confi guration was maintained.

scholarly journals (11aS)-1,5,11,11a-Tetrahydro-1-benzothieno[3,2-f]indolizin-3(2H)-one

2013 ◽  
Vol 69 (12) ◽  
pp. o1819-o1820
Author(s):  
Viktor Vrábel ◽  
Július Sivý ◽  
Peter Šafář ◽  
Jozef Kožíšek
Keyword(s):  
Absolute Configuration ◽  
Structure Determination ◽  
Three Dimensional ◽  
Ring System ◽  
Membered Ring ◽  
Asymmetric Unit ◽  
Framework Structure ◽  
Compound C ◽  
The Mean ◽  
Independent Molecules

The absolute configuration of the title compound, C14H13NOS, was assigned from the synthesis and confirmed by the structure determination. There are two independent molecules in the asymmetric unit. The central six-membered ring of the indolizine moiety adopts an envelope conformation, with the greatest deviations from the mean planes being 0.569 (3) and 0.561 (3) Å for the indolizine bridgehead C atoms of the two molecules. The benzothieno ring attached to the indolizine ring system is planar to within 0.015 (3) Å in both molecules. In the crystal, weak C—H...O and C—H...π interactions lead to the formation of a three-dimensional framework structure.

scholarly journals A Revised Structure and Assigned Absolute Configuration of Theissenolactone A

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4823
Author(s):  
Melissa M. Cadelis ◽  
Soeren Geese ◽  
Lauren Gris ◽  
Bevan S. Weir ◽  
Brent R. Copp ◽  
...  
Keyword(s):  
Absolute Configuration ◽  
Spectroscopic Data ◽  
Structure Elucidation ◽  
Specific Rotation ◽  
Ring System ◽  
Ring Fusion ◽  
Bioassay Guided Fractionation ◽  
Derivatizing Agent ◽  
Chiral Derivatizing Agent ◽  
System 1

Antimicrobial bioassay-guided fractionation of Microcera larvarum led to the isolation of a γ-lactone with a furo[3,4-b]pyran-5-one bicyclic ring system (1) and three known compounds, (3S,4R)-4-hydroxymellein (2), (3S,4S)-4-hydroxymellein (3) and 7-hydroxy-3-(1-hydroxyethyl)isobenzofuran-1(3H)-one (4). Structure elucidation was conducted by NMR spectroscopic methods. Absolute configuration of 1 (2R, 3S, 5S, 7S, 8R) was established using the chiral derivatizing agent MPA and was fully supported by calculated specific rotation and ECD spectra. The spectroscopic data observed for 1 were identical to those previously reported for theissenolactone A (7), necessitating a correction of the latter (from C-5/C-8 trans ring fusion to cis). Compounds 1–4 were evaluated for antimicrobial activity against a panel of pathogens.

scholarly journals Absolute Structure Determination and Kv1.5 Ion Channel Inhibition Activities of New Debromoaplysiatoxin Analogues

Marine Drugs ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. 630
Author(s):  
Sicheng Shen ◽  
Weiping Wang ◽  
Zijun Chen ◽  
Huihui Zhang ◽  
Yuchun Yang ◽  
...  
Keyword(s):  
Absolute Configuration ◽  
2D Nmr ◽  
Ring System ◽  
X Ray Diffraction ◽  
Planar Structures ◽  
Channel Inhibition ◽  
Ic50 Values ◽  
The Absolute ◽  
New Treatments ◽  
Fused Ring System

Potassium channel Kv1.5 has been considered a key target for new treatments of atrial tachyarrhythmias, with few side effects. Four new debromoaplysiatoxin analogues with a 6/6/12 fused ring system were isolated from marine cyanobacterium Lyngbya sp. Their planar structures were elucidated by HRESIMS, 1D and 2D NMR. The absolute configuration of oscillatoxin J (1) was determined by single-crystal X-ray diffraction, and the absolute configurations of oscillatoxin K (2), oscillatoxin L (3) and oscillatoxin M (4) were confirmed on the basis of GIAO NMR shift calculation followed by DP4 analysis. The current study confirmed the absolute configuration of the pivotal chiral positions (7S, 9S, 10S, 11R, 12S, 15S, 29R and 30R) at traditional ATXs with 6/12/6 tricyclic ring system. Compound 1, 2 and 4 exhibited blocking activities against Kv1.5 with IC50 values of 2.61 ± 0.91 µM, 3.86 ± 1.03 µM and 3.79 ± 1.01 µM, respectively. However, compound 3 exhibited a minimum effect on Kv1.5 at 10 µM. Furthermore, all of these new debromoaplysiatoxin analogs displayed no apparent activity in a brine shrimp toxicity assay.

scholarly journals N-Benzyl-3,5-dideoxy-3,5-imino-1,2-O-isopropylidene-β-L-lyxofuranose

2012 ◽  
Vol 68 (8) ◽  
pp. o2410-o2410
Author(s):  
David S. Edgeley ◽  
Sarah F. Jenkinson ◽  
Gabriel Lenagh-Snow ◽  
Catherine Rutherford ◽  
George W. J. Fleet ◽  
...  
Keyword(s):  
Absolute Configuration ◽  
Title Compound ◽  
Ring System ◽  
Starting Material ◽  
X Ray ◽  
X Ray Crystallography ◽  
Compound C ◽  
Relative Stereochemistry ◽  
The Absolute

X-ray crystallography confirmed the formation, structure and relative stereochemistry of the title compound, C15H19NO3, which contains a sterically congested four-membered azetidine ring system. The absolute configuration was determined by the use of L-arabinose as the starting material.

Alkaloids of Schelhammera pedunculata (Liliaceae). II. Reactions of schelhammeridine

1969 ◽  
Vol 22 (10) ◽  
pp. 2203 ◽  
Author(s):  
SR Johns ◽  
JA Lamberton ◽  
AA Sioumis ◽  
H Suares
Keyword(s):  
Acetic Acid ◽  
Hydrochloric Acid ◽  
Acetic Anhydride ◽  
Absolute Configuration ◽  
Acetic Acid Solution ◽  
Acetyl Derivative ◽  
Major Product ◽  
Ring System ◽  
Single Isomer ◽  
Formed Product

Catalytic hydrogenation of schelhammeridine (I) in acetic acid solution gives demethoxydihydroschelhammeridine (II), 1,2,6α,7- tetrahydroschelhammeridine (III), dihydroschelhammeridine (IV), and a tetrahydro derivative (V), the formation of which involves cleavage of the C5-N9 bond. The major product from heating schelhammeridine with 10% aqueous hydrochloric acid is the alcohol (VIIa) with the configuration at C 3 opposite to that in schelhammeridine. Other products are the alcohol (IX) and two amino alcohols (Xa) and (XIIa) which have a diphenyl ring system formed by the aromatization of ring A. The compounds (Xa) and (XIIa) have been shown to be diastereoisomers with the same absolute configuration for the dissymmetric diphenyl system, but the opposite configuration at C 7, and they have been characterized as N-acetyl derivatives (Xb) and (XIIb) which have been assigned the respective configurations shown in (XX) and (XVIII). On heating with acetic anhydride, schelhammeridine is converted into the N,O-diacetyl compound (XVa) which on hydrolysis affords (XVb), the optical antipode of (Xb). All three stereo-isomeric N-acetylamides (Xb), (XIIb), and (XVb), are oxidized to the same optically inactive ketone (XI). A mechanism for the acetic anhydride reaction that explains the formation of only a single isomer is discussed, and it has been shown that the formation of (XVa), enantiomeric with (Xc), in this reaction necessarily involves inversion of the configuration of the diphenyl system in the first-formed product, which must be the O-acetyl derivative of (XVIII). It is concluded that amide alcohols (XVIII) and (XX) retain the configuration for the diphenyl system that would be predicted from the known absolute configuration of schelhammeridine, but that the initially formed O-acetyl derivative of (XVIII) obtained in the reaction with acetic anhydride is converted quantitatively at the temperature of the reaction mixture into the O-acetyl derivative of (XXI) by inversion of the diphenyl configuration.

Stochasting modeling of planetary ring systems

1984 ◽  
Vol 75 ◽  
pp. 461-469 ◽  
Author(s):  
Robert W. Hart
Keyword(s):  
Maximum Entropy ◽  
Ring System ◽  
The Sun ◽  
Ultimate State ◽  
Interparticle Interactions ◽  
Ring Systems ◽  
First Order ◽  
Planetary Ring ◽  
Insight Into

ABSTRACTThis paper models maximum entropy configurations of idealized gravitational ring systems. Such configurations are of interest because systems generally evolve toward an ultimate state of maximum randomness. For simplicity, attention is confined to ultimate states for which interparticle interactions are no longer of first order importance. The planets, in their orbits about the sun, are one example of such a ring system. The extent to which the present approximation yields insight into ring systems such as Saturn's is explored briefly.

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