Polyhydroxylated pyrrolizidines. Part 6: A new and concise stereoselective synthesis of (+)-casuarine and its 6,7-diepi isomer, from DMDP

Synthetic and spectroscopic studies on the structures of uniflorines A and B: structural revision to 1,2,6,7-tetrahydroxy-3-hydroxymethylpyrrolizidine alkaloids

“…On this assumption we have reassigned the published 1 H NMR data for uniflorine A as shown in Table 3 by analogy with the known chemical shifts, coupling constants and assignments for casurine 28. 27 A comparison of this reassigned NMR data for uniflorine A with that of casuarine 28 and its known synthetic diastereomers, 7-epi-28 30 and 6,7-di-epi-28 30,31 ( Figure 3) indicated that these three compounds were clearly different. However, their 1 H NMR spectral data showed a much better correlation than that between the reported data for uniflorine A and the epimerc 1,2,6,7,8-pentahydroxyindolizidines shown in Table 1.…”

“…Analysis of the 13 C NMR chemical shifts for casuarine 28, 27 7-epi-28 30 and 6,7-di-epi-28 31 and that reported for uniflorine A 1 (Table 5) Original assignments based on an indolizidine structure. 1…”

Synthetic Strategies towards the Azabicyclo[3.3.0]-Octane Core of Natural Pyrrolizidine Alkaloids. An Overview

“…Thus an intramolecular reaction of the ester with an NH-unprotected pyrrolidine generates a PA-core as an amide in the first step, and is generally followed by reductive removal of the oxygen atom of the amide bond in the second stage followed usually by deprotection steps to deliver the final PAs (Scheme 9). This route provided PAs from the hyacinthacine family 120,152-162 as well as absouline, [163][164][165] isoretronecanol, 166,167 pyrrolam A, 168,169 trachelanthamidine, 170,171 casuarine, 158,172,173 heliotridane, 175 turneforcidine 175 and a fungi PA -7a(S)-phydroxyphenopyrrozin. 176 Typical yields for the cyclization step were in the range from 22% to quantitative.…”

Polyhydroxylated Pyrrolizidines. Part 7. Stereoselective Synthesis of Unnatural Analogs of (+)‐Casuarine from Partially Protected DGDP

“…Recently, we reported on the stereoselective synthesis of (þ)-casuarine (1), [1] which together with hyacinthacine C 1 [4] are the polyhydroxylated pyrrolizidinic alkaloids (PHPAs) with the highest degree of hydroxylation found in nature so far. In addition, and continuing with our efforts [1,5] on the preparation of PHPAs, we are interested in exploring the possibility of preparing other unnatural synthetic isomers of 1 at the starred positions that could be of interest for structure-activity relationship studies on glycosidase inhibition.…”

“…In addition, and continuing with our efforts [1,5] on the preparation of PHPAs, we are interested in exploring the possibility of preparing other unnatural synthetic isomers of 1 at the starred positions that could be of interest for structure-activity relationship studies on glycosidase inhibition. According to Figure 1, construction of the target PHPAs 2 could be achieved as follows: ring A comes from an orthogonally protected derivative 3 of 2,5-dideoxy-2,5-imino-D-glucitol (DGDP), which transfers its inherent chirality to the final compound, whereas the B ring, with the appropriate stereochemistry and functionalization, would be built up following the synthetic route outlined in Scheme 1, consisting of a carbon-chain lengthening at C(5 0 ) of (2S,3R,4R,5R)-3,4-dibenzyloxy-2 0 -O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine (3), stereocontrolled dihydroxylation, and finally cyclization to the pyrrolizidine skeleton.…”