520-61-6

Upstream product

• 520-65-0 rosmarinine 
• 85781-35-7 Methanesulfonic acid (2S,3S)-2,4-bis-methoxymethoxy-3-((2R,3R)-3-methoxymethoxy-5-oxo-pyrrolidin-2-yl)-butyl ester 
• 85781-32-4 (4R,5R)-5-((1S,2S)-3-Hydroxy-1-hydroxymethyl-2-methoxymethoxy-propyl)-4-methoxymethoxy-pyrrolidin-2-one 
• 696592-45-7 1-ethoxyvinyl ethyl maleate 
• 85781-33-5 (4R,5R)-5-((1S,2S)-3-Hydroxy-2-methoxymethoxy-1-methoxymethoxymethyl-propyl)-4-methoxymethoxy-pyrrolidin-2-one 
• 163982-25-0 4-Nitro-benzoic acid (2S,2aR,3S,7aR,7bR)-2-methoxy-4-oxo-octahydro-furo[2,3,4-gh]pyrrolizin-3-yl ester 
• 163982-24-9 (2S,2aR,3R,7aR,7bR)-3-Hydroxy-2-methoxy-hexahydro-furo[2,3,4-gh]pyrrolizin-4-one 
• 163982-23-8 (2S,2aR,3R,7aR,7bR)-2,3-Dihydroxy-hexahydro-furo[2,3,4-gh]pyrrolizin-4-one 
• 338746-33-1 methyl (2aR,3S,6aR,6bR)-2-oxo-hexahydro-1,4-dioxa-4a-aza-cyclopenta[cd]pentalene-3-carboxylate 
• 855596-40-6 ethyl (2aR,2a¹R,3S,6aR)-2-oxohexahydro-1,4-dioxa-4a-azacyclopenta[cd]pentalene-3-carboxylate 
• 338746-34-2 (2aR,3S,7aR,7bR)-3-hydroxy-2,4-dioxo-octahydro-furo[2,3,4-gh]pyrrolizine 
• 85781-31-3 (3R,4R,5S,6S)-4-Benzyloxycarbonylamino-7-(tert-butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-3,6-bis-methoxymethoxy-heptanoic acid methyl ester 
• 1027640-30-7 (3R,4R,5S,6S)-4-Benzyloxycarbonylamino-7-(tert-butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-3,6-dihydroxy-heptanoic acid 

Relevant academic research and scientific papers

Lipase-catalyzed domino kinetic resolution of α-hydroxynitrones/ intramolecular 1,3-dipolar cycloaddition: A concise asymmetric total synthesis of (-)-rosmarinecine

The title domino reactions were developed to directly provide tetrahydrofuro[3,4-c]isoxazole derivatives (5 and 9) in ≥ 90% ee from racemic α-hydroxynitrones (2 and 6), which were used in the concise asymmetric total synthesis of (-)-rosmarinecine 10. The Royal Society of Chemistry 2005.

Protecting-group-free catalytic asymmetric total synthesis of (-)-rosmarinecine

The protecting-group-free asymmetric total synthesis of (-)-rosmarinecine was achieved in only four steps from the commercially available (±)-3-hydroxypyrrolidine hydrochloride (2a). The key steps include the direct oxidation of (±)-2a to (±)-3-hydroxy-1-pyrroline N-oxide (1a) using the Davis reagent and the domino reaction; viz., the lipase-catalyzed dynamic kinetic resolution of (±)-1a with 1-ethoxyvinyl ethyl maleate followed by the intramolecular [3+2] dipolar cycloaddition reaction of the generated optically active ester. Some insights into the mechanism of the racemization of the optically active 1a, observed during the enzymatic process, were also obtained.

Total synthesis of (-)-rosmarinecine by intramolecular cycloaddition of (S)-malic acid derived pyrroline N-oxide

(equation presented) Straightforward total syntheses of (-)-rosmarinecine have been achieved from L-malic acid derived pyrroline N-oxides by two novel useful cascade processes, which join the family of domino reactions. Both strategies, which furnished the target alkaloid in enantioenriched and enantiopure forms, respectively, allow complete control of configuration at all the three newly created contiguous stereogenic centers.

Tandem [4+2]/[3+2] cycloadditions of nitroalkenes. 9. Synthesis of (-)-rosmarinecine

(-)-Rosmarinecine (2) is the necine base portion of the pyrrolizidine alkaloid (-)-rosmarinine. (-)Rosmarinecine is a representative of the group of pyrrolizidines that show a cis relationship between adjacent stereocenters C(1), C(7), and C(7a), in addition to a highly oxygenated skeleton. (-)-Rosmarinecine (2) has been synthesized in eight steps and 14.8% overall yield, as an illustration of a general approach for the construction of pyrrolizidines having this stereochemical feature. The key step in the asymmetric synthesis is a Lewis acid-promoted, tandem inter-[4+2]/intra-[3+2] cycloaddition between a fumaroyloxy nitroalkene and a chiral vinyl ether.

Pyrrolizidine Alkaloid Biosynthesis. Synthesis of 3H-Labelled Trachelanthamidine and Isoretronecanol and their Incorporation into Three Pyrrolizidine Bases (Necines)

(+/-)-Isoretronecanol (22) and (+/-)-trachelanthamidine (24) were prepared by 1,3-dipolar cycloaddition of N-formylproline with ethyl propiolate followed by reduction steps.These 3H-labelled 1-hydroxymethylpyrrolizidines together with putrescine were fed to Senecio isatideus which produces retrorsine (1); S. pleistocephalus which yields rosmarinine (8); and Cynoglossum officinale which affords echinatine (5).The double labelling experiments demonstrated that isoretronecanol is incorporated much more efficiently into rosmarinine than into retrorsine or echinatine, whereas trachelanthamidine is a much more efficient precursor for retrorsine and echinatine.Base hydrolysis of retrorsine and echinatine labelled with trachelanthamidine and of rosmarinine labelled with isoretronecanol established that most of the 3H-label was in the base portions, retronecine (2), heliotridine (6), and rosmarinecine (9), respectively.Further degradation of retronecine and rosmarinecine showed that most of the radioactivity was confined to the β-alanine (4) portion.The biosynthetic pathways to isoretronecanol and trachelanthamidine apparently diverge prior to the formation of these 1-hydroxymethylpyrrolizidines, probably during the cyclisation of an immonium ion (14) to form the 1-formylpyrrolizidines (15) and (17).