The Sulfinyl Moiety as an Internal Nucleophile. 2. Stereoselective Synthesis of (−)-Galantinic Acid via 1,3-Asymmetric Induction

Abstract

A stereoselective synthesis of (-)-galantinic acid is disclosed. The key steps include hydrolytic kinetic resolution of a racemic epoxide and regio- and stereoselective heterofunctionalization of an olefin, using a pendant sulfinyl group as the nucleophile. The participation of the sulfinyl group was unambiguously proven by conducting the reaction in the presence of H(2)(18)O.

Catalytic Non‐Enzymatic Kinetic Resolution

“…Among the advantages of the hydrolytic KR process are its broad applicability over a range of simple as well as functionalized terminal epoxides, high enantioselectivity, remarkable practical appeal, and low catalyst loading. Unsurprisingly, the generality and broad substrate specificity of Jacobsen’s hydrolytic KR methodology has been exploited for the production of a wide range of chiral synthons for natural products and bioactive compounds synthesis, including recent strategies directed towards the synthesis of cytochalasin B,122 apicularen A,123 ( S )‐timolol,124 decarestrictine D,125 cryptocarya diacetate,126 (2 S ,3 R )‐4‐hydroxyornithine,127 (+)‐negamycin,128 (−)‐ cis ‐lauthisan and (+)‐isolaurepan,129 herbarumin III,130 (−)‐deoxoprosopinine,131 ( S )‐atenolol,132 tarchonanthuslactone,133 aspinolide A,134 massoialactone,135 ( R )‐tuberculostearic acid,136 dihydrobenzofurans,137 ( S )‐vigabatrin and ( S )‐dihydrokavain,138 1‐deoxy‐5‐hydroxyshingosine analogues,139 (+)‐patulolide C,140 (+)‐bataxolol,141 (+)‐diplodialides , B and C,142 ( R )‐mexiletine,143 (+)‐allosedamine,144 ( S )‐metoprolol and ( S )‐betaxolol,145 enciprazine,146 and C 13 –C 22 of amphidinolide T2,147 amphidinolide T1,148 iso ‐cladospolide B and cladospolide B,149 anti‐inflammatory agent (7 S ,17 S )‐resolvin D5,150 ( S )‐ and ( R )‐naftopidil,151 neocarazostatin,152 nonactin,153 elecanacin,154 (+)‐peloruside,155 spongiacysteine,156 astrocyte activation suppressor ONO‐2506,157 (−)‐indolizidine 223AB,158 (7 S ,16 R ‐17S)‐resolvin D2,159 (−)‐galantinic acid,160 (+)‐Sch 642305,161 (4 R )‐hydroxy analogues of Annonaceous acetogenins,162 insect pheromones,163 hNK‐1 receptor antagonist,164 L ‐carnitine,165 and (+)‐brefeldin A 166. The use and range of chiral epoxides resolved in these natural or bioactive product syntheses clearly stands as a testament to the true power of Jacobsen’s hydrolytic KR as a routine methodology for stereoselective organic synthesis, as shown in Figure 5.…”

Formal Synthesis of Galantinic Acid by Oxo‐Diels–Alder Methodology

“…Most of the reported methodologies are based on a chiral pool approach 5. Only two approaches utilize enantioselective processes – Jacobsen's hydrolytic kinetic resolution of epoxides6a and the Sharpless epoxidation6b – but they suffer from low overall yields (5.6 and 5.7 %, respectively).…”

First Enantioselective Synthesis of Surinamensinol B and a Non‐Natural Polysphorin Analogue by a Two‐Stereocentered Hydrolytic Kinetic Resolution

“…Hz, 2 H) ppm 13. C NMR (50 MHz, CDCl 3 ): δ = 21.4, 55.8, 55.9, 60.6, 70.5, 72.2, 78.0, 94.4, 104.2, 127.8, 129.7, 132.6, 132.7, 137.5, 144.8, 153.2 ppm.…”

“…

An efficient and economical approach to the synthesis of antitumor and anti-inflammatory surinamensinol B (1) and antimalarial polysphorin analogue 2 has been achieved with high enantiomeric purity (96 % ee) by starting from commercially available 3,4,5-trimethoxybenzaldehyde. [13] The LiAlH 4 reduction of ester 8 produced the corresponding alcohol 9 (93 % yield), which was protected as its tosylate [TsCl (Ts = p-tolylsulfonyl), Et 3 N, CH 2 Cl 2 , room temp., 3 h] to give 10. Co III -catalyzed hydrolytic kinetic resolution (HKR) to give syn-alkoxy epoxide.

Our synthesis began with 3,4,5-trimethoxybenzaldehyde (5), which was subjected to a two-carbon Wittig olefination by using Ph 3 P=CHCO 2 Et to give cinnamate ester 6 in 98 % yield.

…”

“…1 H NMR (500 MHz, CDCl 3 ): δ = 1.36 (d, J = 6.4 Hz, 3 H), 1.88 (quint, J = 6.7 Hz, 2 H), 2.63 (t, J = 7.9 Hz, 2 H), 3.37 (s, 3 H), 3.43 (s, 3 H), 3.54 (t, J = 6.41 Hz, 2 H), 3.78 (s, 3 H), 3.83 (s, 3 H), 3.85 (s, 6 H), 4.41 (quint, J = 5.8 Hz, 1 H), 4.63 (s, 2 H), 4.67 (q, J = 6.7 Hz, 2 H), 4.76 (d, J = 5.2 Hz, 1 H), 6.63-6.69 (m, 5 H) ppm 13. 1,2,3-Trimethoxy-5-[(1S,2R)-2-{2-methoxy-4-[3-(methoxymethoxy)propyl]phenoxy}-1-(methoxymethoxy)propyl]benzene (23): To a stirred solution of chiral alcohol 16 (100 mg, 0.35 mmol), PPh 3 (91.49 mg, 0.35 mmol), and diisopropyl azodicarboxylate (70.9 mg, 0.35 mmol) in THF (5 mL) at 0°C was added 2-methoxy-4-[3-(methoxymethoxy)propyl]phenol (22; 78.54 mg, 0.35 mmol).…”