Indolizidine 167B Research Articles

Arylation of Cyclopropanol with Pyrrole: Asymmetric Synthesis of Indolizidine 167B, Indolizidine 209D, and Monomorine I

A Fe(NO3)3-mediated ring-opening arylation of cyclopropanol with the electron-rich pyrrole has been developed, which might proceed through oxidative radical ring opening of cyclopropanol followed by cyclization to the pyrrole motif and then aromatization. This method enables direct arylation of cyclopropanol without prefunctionalization and thus allows rapid access to a diverse array of chiral 5,6,7,8-tetrahydroindolizines from easily available chiral amino acid esters. The synthetic utility has been demonstrated by the asymmetric synthesis of alklaoids (-)-indolizidine 167B, (+)-indolizidine 209D, (+)-monomorine I, and a natural product analogue.

Au-catalyzed stereodivergent synthesis of 2,5-disubstituted pyrrolidines: total synthesis of (+)-monomorine I and (+)-indolizidine 195B.

Stereodivergent synthesis of 2,5-disubstituted pyrrolidines was achieved via a Au-catalyzed tandem intramolecular alkyne hydroamination/iminium formation/Et3SiH reduction. Importantly, the stereochemical outcome could be switched by choosing an appropriate nitrogen protecting group. Total synthesis of a diastereomeric pair of alkaloid natural products, monomorine I and indolizidine 195B, was achieved to showcase the synthetic utility of the tandem reaction.

Stereodivergent Total Syntheses of (+)‐Monomorine I and (+)‐Indolizidine 195B

AbstractA simple and efficient stereoselective total syntheses of two natural products (+)‐monomorine I and (+)‐indolizidine 195B in high yields starting from a readily available alcohol is described. The key step in this synthetic route exploits the judicious use of solvent to enable a closed or open transition state in a nucleophilic addition of Grignard reagent to sulfinimine, giving selective access to two distinct diastereomers required for the formation of the two target natural products.

The Study of Several Synthesis Methods of Indolizidine (±)-209I and (±)-209B as Natural Alkaloids

Natural products have received much attention due to their importance and application. Indolizidine, categorized as an alkaloid, has several biological activities. The synthesis of natural compounds such as indolizidines has attracted much attention from many chemists’ and researchers’ perspectives. There are many areas to be explored in this subject; that is why synthesizing indolizidine 209I and (±)-indolizidine 209B as natural compounds have received much consideration. This review discloses the procedures and methodology to provide (±)-indolizidine 209I and 209B due to the importance of indolizidines.

Recent Progress Towards Synthesis of the Indolizidine Alkaloid 195B

Natural products have been received attention due to their importance in human life as those are biologically active. In this review, there are some reports through different methods related to the synthesis of the indolizidine 195B which was extracted from poisonous frog; however, due to respect nature, the synthesis of natural compounds such as indolizidine has been attracted much attention among scientists and researchers. This review discloses the procedures and methods to provide indolizidine 195B from 1989 to 2018 due to their importance as a natural product. There are several methods to give rise to the indolizidine 195B as a natural product that is highly active from the biological perspective in pharmaceutical chemistry. In summary, many protocols for the preparations of indolizidine 195B from various substrates, several reagents, and conditions have been reported from different aromatic and aliphatic.

Catalytic protodeboronation of pinacol boronic esters: formal anti-Markovnikov hydromethylation of alkenes.

Pinacol boronic esters are highly valuable building blocks in organic synthesis. In contrast to the many protocols available on the functionalizing deboronation of alkyl boronic esters, protodeboronation is not well developed. Herein we report catalytic protodeboronation of 1°, 2° and 3° alkyl boronic esters utilizing a radical approach. Paired with a Matteson-CH2-homologation, our protocol allows for formal anti-Markovnikov alkene hydromethylation, a valuable but unknown transformation. The hydromethylation sequence was applied to methoxy protected (-)-Δ8-THC and cholesterol. The protodeboronation was further used in the formal total synthesis of δ-(R)-coniceine and indolizidine 209B.

Loss of skin alkaloids in poison toads, Melanophryniscus klappenbachi (Anura: Bufonidae) when fed alkaloid-free diet

Toads of the genus Melanophryniscus contain toxic alkaloids sequestered from a diet of mainly ants and mites. Wild-caught specimens of M. klappenbachi were fed an alkaloid-free diet and their alkaloid profile was analyzed during 38 months in captivity. Individual alkaloid patterns varied considerably. Over time, the concentration of two alkaloids, pumiliotoxin 251D and 3,5-disubstituted indolizidine 195B, significantly declined, suggesting that the toads depend on continuous access to alkaloid-containing prey to maintain natural levels of their chemical defense.

Reductive Alkylation of Tertiary Lactams via Addition of Organocopper (RCu) Reagents to Thioiminium Ions

A simple procedure for the conversion of tertiary lactams to 2-monoalkylated cyclic amines is described. The reaction sequence involves conversion of a lactam to a thioiminium ion followed by reaction with an organocopper (RCu) reagent and final reduction with triacetoxyborohydride. The reaction is high yielding and shows an excellent functional group tolerance. Its utility is demonstrated by a rapid synthesis of indolizidine 167B. The excellent chemoselectivity of the process, where only monoalkylation products are formed, is rationalized by a mechanism involving the formation of a transient enamine.

ChemInform Abstract: Formal Synthesis of (.+‐.)‐Indolizidine 209B.

Abstract A new method for the synthesis of cis -C-8 methylated indolizidines and quinolizidines has been developed. Straightforward transformations including an isomerization to the trans configuration led to a formal synthesis of (±)-indolizidine 209B.

Formal synthesis of (±)-indolizidine 209B

A new method for the synthesis of cis-C-8 methylated indolizidines and quinolizidines has been developed. Straightforward transformations including an isomerization to the trans configuration led to a formal synthesis of (±)-indolizidine 209B.

ChemInform Abstract: Radical Azidation Reactions and Their Application in the Synthesis of Alkaloids

AbstractReview: 49 refs.

Radical azidation reactions and their application in the synthesis of alkaloids

Recent advances in radical azidation using sulfonyl azides are presented. For instance, radical carboazidation using α-iodoketones, desulfitative carboazidation, and anti-Markovnikov hydroazidation of alkenes are described. These novel methods tolerate a large number of functional groups and allow the synthesis of organic azides that would be difficult to synthesize otherwise. The transformation of the azides using reductive processes as well as a Schmidt reaction under nonacidic conditions were used to synthesize alkaloids including indolizidine 167B, monomorine I, cylindricine C, and lepadiformine C.

Chiral synthesis of indolizidines 209D and 167B via asymmetric oxidation of sulfides and sulfoxides

Chiral synthesis of indolizidine natural products (−)-209D and (−)-167B, as well as their antipodes, has been achieved through asymmetric oxidation of racemic thio-substituted indolizidines to the chiral sulfoxides and sulfones followed by Raney nickel reduction.

Total synthesis of (−)-indolizidine 167B via an unusual Wolff rearrangement from an α,β-unsaturated diazoketone

A concise synthesis of the (−)-indolizidine alkaloid 167B and two formal syntheses of (−)-indolizidine 209D and (−)-coniceine are described in just three steps from an α,β-unsaturated diazoketone, via an unusual photochemical Wolff rearrangement. Preparation of the unsaturated diazoketone is straightforward from N-Cbz-prolinal and a 3-diazo-2-oxopropylphosphonate, employing a Horner–Wadsworth–Emmons reaction. The strategy should be feasible and easily adaptable to the synthesis of other indolizidine alkaloids and analogues.

Enantioselective access to (−)-indolizidines 167B, 209D, 239AB, 195B and (−)-monomorine from a common chiral synthon

An enantioselective access to (−)-indolizidine alkaloids 167B, 209D, 239AB, 195B and (−)-monomorine from a new chiral synthon is described. The use of (S)-3-(Cbz-amino)-4-(tert-butyldimethylsilyloxy)butanal, obtained from l-aspartic acid, has provided efficient access of the indolizidine frame work through a Horner–Wadsworth–Emmons reaction and reductive cyclization as the key steps.

Total syntheses of (+)-monomorine I and (−)-indolizidine 195B from sulfinimine-derived 3-oxo pyrrolidine 2-phosphonates

Indolizidine alkaloids (+)-monomorine I ( 1) and (−)-indolizidine 195B ( 2), having cis and trans relationships of the C-3 and C-9 substituents, respectively, were prepared from the sulfinimine-derived chiral building blocks N-sulfinyl δ-amino β-ketophosphonate and 3-oxo pyrrolidine 2-phosphonate.

ChemInform Abstract: Stereoselective Synthesis of (.+-.)-Indolizidines 167B, 205A, and 207A. Enantioselective Synthesis of (-)-Indolizidine 209B.

The racemates of indolizidine 167B (X), 205A (XVI) and 207A (XVII) as well as (-)-indolizidine 209B (XXVI) are prepared as shown using a general strategy.

ChemInform Abstract: Asymmetric Synthesis of the Indolizidine Alkaloids 207A, 209B, and 235B′: 6-Substituted 2,3-Didehydropiperidine-2-carboxylate as a Versatile Chiral Building Block.

The asymmetric synthesis of 5-substituted 8-methylindolizidines 1-3 was achieved via the highly stereocontrolled Michael reaction of the title compound 5

Intramolecular Schmidt Reaction Involving Primary Azidoalcohols under Nonacidic Conditions: Synthesis of Indolizidine (−)-167B

A powerful intramolecular Schmidt reaction starting from primary azidoalcohols is reported. This approach involves a nonacidic activation of the alcohol via triflation. The synthetic potential offered by the mild reaction conditions is demonstrated by a highly selective synthesis of (-)-indolizidine 167B.

A Concise Synthesis of (−)‐Indolizidines 209D and 209B

AbstractA general stereoselective synthetic route to 5‐substituted and 5,8‐disubstituted indolizidine alkaloids has been developed starting from commercially available L‐proline. (−)‐Indolizidines 209D and 209B were efficiently synthesized in 9.8% and 14.8% overall yields in seven and five‐step reactions from readily available aldehyde 3 and ketone 10, respectively. The key steps of this synthesis involve a substrate‐induced asymmetric addition of ethyl lithiopropiolate to aldehyde 3 or methyl ketone 10, and a two‐step one‐pot hydrogenation/cyclization sequence to construct the bicyclic skeleton.