First Total Synthesis of Pamamycin-621D

Aim and Objective: The objective of our work was to synthesize and fully characterize Pamamycin- 621D, one of the less abundant members of a large family of macrodiolides with antimycobacterial properties, which had never been synthesized before. Furthermore, we also wished to improve our general strategy by using a new unsaturated precursor. Materials and Method: A new unsaturated ethylketone precursor was prepared using alkene cross metathesis, and a convergent and flexible strategy based on a key diastereoselective aldol addition was implemented to afford pamamycin-621D in 12 steps from that precursor. Results: Pamamycin-621D has been obtained and fully characterized for the first time. The structure of pamamycin-621D was confirmed by HRMS and comparison of 1H-NMR spectra with the natural pamamycin- 621D. Both optical rotation and 13C-NMR had not been published previously due to lack of material, and the latter are reported here for the first time. Given the scarce characterization available previously, our synthesis also gives additional support to the initial structural assignment of pamamycin-621D. A significant improvement of the key aldol addition via the use of a new unsaturated precursor is also reported. Conclusion: The work described above constitutes the first total synthesis of pamamycin-621D and has enabled us to fully characterize this scarcely available natural product. More importantly, this work highlights the fact that our synthetic approach provides ready access to various members of the pamamycin family, allowing possible studies on structure-activity relationships and mode of action of even the least abundant of these natural products. The synthesis of other pamamycin congeners and biological investigations will be published in due course.

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The Total Synthesis of Rhabdastrellic Acid A

10.26434/chemrxiv.7479944 ◽

2018 ◽

Author(s):

Yaroslav Boyko ◽

Christopher Huck ◽

David Sarlah

Keyword(s):

Total Synthesis ◽

Late Stage ◽

Cross Coupling ◽

Side Chains ◽

General Strategy ◽

Modular Approach ◽

Linear Sequence ◽

Generating Sequence ◽

First Time

<div>The first total synthesis of rhabdastrellic acid A, a highly cytotoxic isomalabaricane triterpenoid, has been accomplished in a linear sequence of 14 steps from commercial geranylacetone. The prominently strained trans-syn-trans-perhydrobenz[e]indene core characteristic of the isomalabaricanes is efficiently accessed in a selective manner for the first time through a rapid, complexity-generating sequence incorporating a reductive radical polyene cyclization, an unprecedented oxidative Rautenstrauch cycloisomerization, and umpolung 𝛼-substitution of a p-toluenesulfonylhydrazone with in situ reductive transposition. A late-stage cross-coupling in concert with a modular approach to polyunsaturated side chains renders this a general strategy for the synthesis of numerous family members of these synthetically challenging and hitherto inaccessible marine triterpenoids.</div>

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The Total Synthesis of Rhabdastrellic Acid A

10.26434/chemrxiv.7479944.v1 ◽

2018 ◽

Author(s):

Yaroslav Boyko ◽

Christopher Huck ◽

David Sarlah

Keyword(s):

Total Synthesis ◽

Late Stage ◽

Cross Coupling ◽

Side Chains ◽

General Strategy ◽

Modular Approach ◽

Linear Sequence ◽

Generating Sequence ◽

First Time

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Unified Strategy to Prostaglandins: Chemoenzymatic Total Synthesis of Cloprostenol, Bimatoprost, PGF2α, Fluprostenol, and Travoprost Guided by Biocatalytic Retrosynthesis

10.21203/rs.3.rs-257517/v1 ◽

2021 ◽

Author(s):

Kejie Zhu ◽

Meifen Jiang ◽

Baijun Ye ◽

Guotai Zhang ◽

Weijian Li ◽

...

Keyword(s):

Total Synthesis ◽

Stereoselective Synthesis ◽

Secondary Alcohol ◽

Complex Molecules ◽

Chemical Structures ◽

12 Steps ◽

Diastereoselective Reduction ◽

Stereoselective Oxidation ◽

First Time ◽

Unique Chemical

Abstract Development of efficient and stereoselective synthesis of prostaglandins (PGs) is of utmost importance, owing to their valuable medicinal applications and unique chemical structures. We report here a unified synthesis of PGs cloprostenol, bimatoprost, PGF2α, fluprostenol, and travoprost from the readily available dichloro-containing bicyclic ketone 6a guided by biocatalytic retrosynthesis, in 11-12 steps with 2.9-6.5% overall yields. A Baeyer-Villiger monooxygenase (BVMO)-catalyzed stereoselective oxidation of 6a (99% ee), and a ketoreductase (KRED)-catalyzed diastereoselective reduction of enones 12 (87 : 13 to 99 : 1 dr) were utilized in combination for the first time to set the critical stereochemical configurations under mild conditions. Another key transformation was the copper (II)-catalyzed regioselective p-phenylbenzoylation of the secondary alcohol of diol 10 (3.8 : 1 rr). This study not only provides an alternative route to the highly stereoselective synthesis of PGs, but also showcases the usefulness and great potential of biocatalysis in construction of complex molecules.

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A One-Pot Chemoenzymatic Synthesis of (2S,4R)-4-Methylproline Enables the First Total Synthesis of Antiviral Lipopeptide Cavinafungin B

10.26434/chemrxiv.6405761.v1 ◽

2018 ◽

Author(s):

Christian R. Zwick ◽

Hans Renata

Keyword(s):

Total Synthesis ◽

Natural Product ◽

Complex Molecule ◽

Molecular Target ◽

Chemoenzymatic Synthesis ◽

General Strategy ◽

One Pot

We report an efficient ten-step synthesis of antiviral natural product cavinafungin B in 37% overall yield. By leveraging a one-pot chemoenzymatic synthesis of (2S,4R)-4-methylproline and oxazolidine-tethered (Rink-Boc-ATG-resin) SPPS methodology, the assembly of our molecular target could be conducted in an efficient manner.This general strategy could prove amenable to the construction of other natural and unnatural linear lipopeptides. The value of incorporating biocatalytic steps in complex molecule synthesis is highlighted by this work.

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New Insights into the Nature of the Band Gap of CuGeO3 Nanoparticles: Synthesis, Electronic Structure, and Optical and Photocatalytic Properties

10.26434/chemrxiv.8362409.v1 ◽

2019 ◽

Author(s):

Victor Y. Suzuki ◽

Luís Henrique Cardozo Amorin ◽

Natália H. de Paula ◽

Anderson R. Albuquerque ◽

Julio Ricardo Sambrano ◽

...

Keyword(s):

Electronic Structure ◽

Band Gap ◽

Material Design ◽

Photocatalytic Properties ◽

Critical Parameters ◽

Synthetic Approach ◽

Microwave Assisted ◽

Theoretical Approaches ◽

Nanoparticles Synthesis ◽

First Time

We report, for the first time, new insights into the nature of the band gap of <a>CuGeO3 </a>(CGO) nanocrystals synthesized from a microwave-assisted hydrothermal method in the presence of citrate. To the best of our knowledge, this synthetic approach has the shortest reaction time and it works at the lowest temperatures reported in the literature for the preparation of these materials. The influence of the surfactant on the structural, electronic, optical, and photocatalytic properties of CGO nanocrystals is discussed by a combination of experimental and theoretical approaches, and that results elucidates the nature of the band gap of synthetized CGO nanocrystals. We believe that this particular strategy is one of the most critical parameters for the development of innovative applications and that result could shed some light on the emerging material design with entirely new properties.

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General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

10.26434/chemrxiv.7436795 ◽

2018 ◽

Author(s):

Marc Montesinos-Magraner ◽

Matteo Costantini ◽

Rodrigo Ramirez-Contreras ◽

Michael E. Muratore ◽

Magnus J. Johansson ◽

...

Keyword(s):

Total Synthesis ◽

Asymmetric Synthesis ◽

Chemical Space ◽

Synthetic Approach ◽

Asymmetric Cyclopropanation ◽

Redox Active ◽

Wide Range ◽

Leaving Group ◽

Stereoelectronic Properties ◽

Carbene Transfer

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates and reagents, even when targeting similar compounds. This limits the speed and chemical space available for discovery campaigns. Here we introduce a practical and versatile diazocompound, and we demonstrate its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. We found that the redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect enabled the asymmetric cyclopropanation of a wide range of olefins including unactivated aliphatic alkenes, enabling the 3-step total synthesis of (–)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally-differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons.

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Antiticiombin III Deficiency In A Large Family with 41 Affected Members

10.1055/s-0038-1653102 ◽

1981 ◽

Author(s):

J Stibbe ◽

S Adhin ◽

G L Ong ◽

R S Panday ◽

S H Peters ◽

...

Keyword(s):

Autosomal Dominant ◽

Large Family ◽

Clinical Information ◽

Impedance Plethysmography ◽

Age Group ◽

Oral Contraceptive Pills ◽

Contraceptive Pills ◽

At Iii ◽

L 51 ◽

First Time

Hereditary Antithrombin III (AT III) deficiency was found in a large Hindustani family, living partly in the Netherlands, partly in Suriname. Of 201 members investigated 35 were found to affected: AT III activity (chromogenic substrate) and AT III antigen (immuno-electrophoresis according to Laurell) were about 45 %. Analysis of this fanily clearly demonstrated the autosomal dominant inheritance of the condition. Six non-investigated members (1 living, 5 non-living) were diagnosed as being affected on the basis of affected offspring.Seventeen affected members had no signs of thrombo-embolic(TE) processes (age group 0-10 years old, n=2; 11-20, n=5; 21-30, n=4; 31-40, n=4; 41-50, n=2). Thirteen showed clinical or proven signs of TE processes (first time in age group 0-10 years old, n=0; 11-20, n=l; 21-30, n=G; 31-40, n=4; 41-50,n=l; 51-60, n=0; 61-70, n=l). No clinical information is yet available on the remaining affected members. Deep venous thrombosis (DVT) occurred in 9 patients (age group 21-30, n=5; 31-40, n=3; 61-70, n=l). Triggering factors were none 4, surgery 1, oral contraceptives and preg- nancy4. Pulmonary embolism occurred in 6 patients (2 clinical, 4 proven) and was fatal in 4; ages were 19, 21, 26, 37, 48 and 68 years old. Pregnancy was uncomplicated in 3 women (total of 4 pregnancies), one of these women was treated prophylactically with anticoagulants during pregnancy (1 pregnancy). Two women (9 pregnancies) had a thrombotic episode (1st and 3rd pregnancy respectively) and 1 woman died suddenly 7 days after her 7th childbirth. DVT occurred in 2 of 4 women who used oral contraceptive pills.In some symptomless patients (age 22, 26, 32, 33, 40 years old) impedance plethysmography (n=5), 125I-fibrinogen leg scanning (n=3), 125I-fibrinogen T½(n=3) and 51C-platelet survival (n=l) were normal

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