Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Concise Chemoenzymatic Three Step Total Synthesis of Isosolenopsin Through Medium Engineering.

ABSTRACT: A short and efficient total synthesis of the alkaloid isosolenopsin and its enantiomer has been achieved. In the key step, a ω-transaminase catalyzed the regioselective mono-amination of the diketone pentadecane-2,6-dione which was obtained in a single step via Grignard reaction. Initial low conversions in the biotransformation could be overcome by optimisation of the reaction conditions employing suitable cosolvents. In the presence of 20 vol% DMF or n-heptane best results were obtained employing two enantio-complementary ω-transaminases originating from Arthrobacter between 30-40 °C; under these conditions conversions of >99% and perfect stereocontrol (ee > 99%) were achieved. Diastereostelective chemical reduction (H₂/Pd/C) of the biocatalytic product gave the target compound. The linear three step synthesis provided the natural product isosolenopsin in diastereomerically pure form (ee > 99%, d.r. = 99:1) with an overall yield of 64%.

SUBMITTER: Simon RC

PROVIDER: S-EPMC4151137 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Concise Chemoenzymatic Total Synthesis and Identification of Cellular Targets of Cepafungin I.

Project description:The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin I featuring the use of a regioselective enzymatic oxidation to prepare a key hydroxylated amino acid building block in a scalable fashion. The strategy developed herein enabled access to a chemoproteomic probe, which in turn revealed the exceptional selectivity and potency of cepafungin I toward the β2 and β5 subunits of the proteasome. Further structure-activity relationship studies suggest the key role of the hydroxyl group in the macrocycle and the identity of the lipid tail in modulating the potency of this natural product family. This study lays the groundwork for further medicinal chemistry exploration to fully realize the anticancer potential of cepafungin I.

| S-EPMC8201661 | biostudies-literature

A concise and scalable chemoenzymatic synthesis of prostaglandins.

Project description:Prostaglandins have garnered significant attention from synthetic chemists due to their exceptional biological activities. In this report, we present a concise chemoenzymatic synthesis method for several representative prostaglandins, achieved in 5 to 7 steps. Notably, the common intermediate bromohydrin, a radical equivalent of Corey lactone, is chemoenzymatically synthesized in only two steps, which allows us to complete the synthesis of prostaglandin F2α in five steps on a 10-gram scale. The chiral cyclopentane core is introduced with high enantioselectivity, while the lipid chains are sequentially incorporated through a cost-effective process involving bromohydrin formation, nickel-catalyzed cross-couplings, and Wittig reactions. This cost-efficient synthesis route for prostaglandins holds the potential to make prostaglandin-related drugs more affordable and facilitate easier access to their analogues.

| S-EPMC10957970 | biostudies-literature

The organocatalytic three-step total synthesis of (+)-frondosin B.

Project description:The frondosins are a family of marine sesquiterpenes isolated from the sponge Dysidea frondosa that exhibit biological activities ranging from anti-inflammatory properties to potential application in anticancer and HIV therapy. Herein, a concise enantioselective total synthesis of (+)-frondosin B is described which requires a total of three chemical steps. The enantioselective conjugate addition of a benzofuran-derived boronic acid to crotonaldehyde in the presence of an imidazolidinone organocatalyst builds the critical stereogenic center of frondosin B in the first operation, while the remaining two ring systems of this natural product are installed in the two subsequent steps. A combination of X-ray crystallographic data, deuterium labeling, and chemical correlation studies provides further evidence as to the correct absolute stereochemical assignment of (+)-frondosin B.

| S-EPMC3268339 | biostudies-literature

Enzymatic and Chemoenzymatic Three-Step Cascades for the Synthesis of Stereochemically Complementary Trisubstituted Tetrahydroisoquinolines.

Project description:Chemoenzymatic and enzymatic cascade reactions enable the synthesis of complex stereocomplementary 1,3,4-trisubstituted tetrahydroisoquinolines (THIQs) with three chiral centers in a step-efficient and selective manner without intermediate purification. The cascade employs inexpensive substrates (3-hydroxybenzaldehyde and pyruvate), and involves a carboligation step, a subsequent transamination, and finally a Pictet-Spengler reaction with a carbonyl cosubstrate. Appropriate selection of the carboligase and transaminase enzymes enabled the biocatalytic formation of (1R,2S)-metaraminol. Subsequent cyclization catalyzed either enzymatically by a norcoclaurine synthase or chemically by phosphate resulted in opposite stereoselectivities in the products at the C1 position, thus providing access to both orientations of the THIQ C1 substituent. This highlights the importance of selecting from both chemo- and biocatalysts for optimal results.

| S-EPMC5658969 | biostudies-literature

A Concise Total Synthesis of (±)-Vibralactone.

Project description:Disclosed is a five-step synthesis of (±)-vibralactone, a biologically active terpenoid natural product. A key photochemical valence isomerization of 3-prenyl-pyran-2-one produces both the all-carbon quaternary stereocenter and the ?-lactone at an early stage. Cyclopropanation of the resulting bicyclic ?-lactone produces a strained housane structure that is converted to the natural product through a sequential ring expansion and reduction strategy. This concise and modular route to the natural product provides the shortest total synthesis of (±)-vibralactone reported to date.

| S-EPMC6351154 | biostudies-literature

Concise, enantioselective total synthesis of (-)-alstonerine.

Project description:A novel enantioselective total synthesis of (-)-alstonerine has been completed that requires only 15 steps from L-tryptophan. The synthesis features the first application of a Pauson-Khand reaction to synthesize an azabridged bicyclic skeleton. [reaction: see text]

| S-EPMC2516964 | biostudies-literature

Concise total synthesis of (±)-actinophyllic acid.

Project description:A concise total synthesis of the complex indole alkaloid (±)-actinophyllic acid was accomplished by a sequence of reactions requiring only 10 steps from readily-available, known starting materials. The approach featured a Lewis acid-catalyzed cascade of reactions involving stabilized carbocations that delivered the tetracyclic core of the natural product in a single chemical operation. Optimal conversion of this key intermediate into (±)-actinophyllic acid required judicious selection of a protecting group strategy.

| S-EPMC4034156 | biostudies-literature

Concise two-step chemical synthesis of molnupiravir.

Project description:A concise synthesis of molnupiravir in a one-pot two-step approach starting from uridine is described. Formally, herein, two sets of one-pot two-reaction steps introducing simplicity for purifications and using chemically available reagents are presented. In this context, molnupiravir was obtained in up to 68% overall yield and multigram-scale. In addition, HPLC analysis showed the molnupiravir purity above 99%.

| S-EPMC9585438 | biostudies-literature

A concise asymmetric total synthesis of (+)-brevisamide.

Project description:A new protecting-group-free synthesis of the marine monocyclic ether (+)-brevisamide is reported. The enantioselective synthesis utilizes a key asymmetric Henry reaction and an Achmatowicz rearrangement for the formation of the tetrahydropyran ring. A penultimate Stille cross-coupling allows for an efficient installation of the conjugated (E,E)-diene side chain ultimately delivering (+)-brevisamide.

| S-EPMC3365585 | biostudies-literature

A concise total synthesis of saliniketal B.

Project description:We report a concise, enantioselective, and highly efficient synthesis of the marine actinomycete-derived natural product saliniketal B. Our approach was motivated with an eye toward future structure-function studies of this inhibitor of phorbol ester-mediated ornithine decarboxylase induction via an unknown mechanism. Our strategy highlights the utility of Pt(II)-mediated cycloisomerization of alkynediols developed in our laboratory to construct the dioxabicyclo[3.2.1]octane ring system, a highly selective aldol fragment coupling whose stereochemical outcome is influenced by a gamma-stereogenic methyl group, and an interesting one-pot desilylation/dihydropyranone fragmentation/amidation sequence. As such, saliniketal B was obtained in 11 steps and 23% overall yield from commercially available starting material via a convergent coupling of two equally complex fragments assembled in seven and eight steps (39 and 45%), respectively.

| S-EPMC2754317 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data