Thieme Chemistry Journal Awardees - Where Are They Now? Approaches to Tagetitoxin and its Decarboxy Analogue from d-Glucose

Abstract

A fifteen-step route has been developed from 1,6-anhydro-β-d-glucopyranose to a C-alkynyl glycoside precursor of decarboxytagetitoxin. Preparation of 1,6-anhydro-5-C-vinyl-β-d-gluco-pyranose, a potential precursor of tagetitoxin, is also described.

Key words

carbohydrates - natural products - stereoselective synthesis - alkynes - organometallic reagents

References and Notes

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12

Data for Selected Compounds
3-Azido-4,6- O -benzylidene-1- O - tert -butyldimethyl-silanyl-3-deoxy-1,1-di- C -(trimethylsilanylethynyl)- d -altritol (11)
[α]_D ^²0 -72.0 (c 2.35, CH₂Cl₂). IR (CHCl₃ cast): ν_max = 3444, 3055, 2121, 1706, 1421, 1361 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.48-7.43 (3 H, m), 7.36-7.28 (2 H, m), 5.49 (1 H, s), 4.35 (1 H, dd, J = 2.9, 0.9 Hz), 4.21 (1 H, d, J = 2.9 Hz), 4.33 (1 H, dd, J = 11.0, 5.8 Hz), 4.09 (1 H, dddd, J = 10.2, 8.9, 5.8, 2.9 Hz), 3.83 (1 H, dd, J = 9.9, 0.9 Hz), 3.74 (1 H, dd, J = 8.9, 2.9 Hz), 3.63 (1 H, dd, J = 11.0, 10.2 Hz), 3.28 (1 H, d, J = 9.9 Hz), 0.90 (9 H, s), 0.28 (3 H, s), 0.27 (3 H, s), 0.18 (18 H, s). ^¹³C NMR (125 MHz, CDCl₃): δ = 137.4 (C), 129.0 (CH), 128.3 (CH), 126.1 (CH), 103.1 (C), 102.1 (C), 100.1 (CH), 91.6 (C), 91.5 (C), 84.4 (CH), 75.9 (CH), 70.1 (CH₂), 67.1 (C), 63.8 (CH), 60.7 (CH), 25.5 (CH₃), 18.7 (C), -0.5 (CH₃), -0.6 (CH₃), -3.5 (CH₃), -3.6 (CH₃). HRMS-FAB⁺: m/z calcd for C₂₉H₄₇O₅N₃Si₃Na [MNa⁺]: 624.2721; found: 624.2735.
4-Azido-1,3- O -benzylidene-5- O - tert -butyldimethyl-silanyl-4,7,8-trideoxy-8-trimethylsilanyl-β- l - manno -oct-7-yn-2-ulopyranose (12)
[α]_D ^²0 -105.5 (c 0.4, CH₂Cl₂). IR (CHCl₃ cast): ν_max = 3445, 3053, 2304, 1633, 1421 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.47-7.42 (2 H, m), 7.33-7.24 (3 H, m), 5.56 (1 H, s), 4.76 (1 H, d, J = 6.2 Hz), 4.32 (1 H, dd, J = 10.3, 6.2 Hz), 4.23 (1 H, d, J = 2.8 Hz), 4.07 (1 H, dd, J = 10.3, 2.8 Hz), 4.03 (1 H, d, J = 11.9 Hz), 3.74 (1 H, s), 3.69 (1 H, d, J = 11.9 Hz), 0.91 (9 H, s), 0.17 (9 H, s), 0.13 (3 H, s), 0.11 (3 H, s). ^¹³C NMR (125 MHz, CDCl₃): δ = 136.7 (C), 129.0 (CH), 128.2 (CH), 126.0 (CH), 103.0 (C), 100.8 (CH), 95.0 (C), 91.9 (C), 78.9 (CH), 73.5 (CH₂), 67.6 (CH), 66.3 (CH), 58.8 (CH), 25.5 (CH₃), 17.8 (C), -0.5 (CH₃), -4.7 (CH₃), -5.0 (CH₃). HRMS-FAB⁺: m/z calcd for C₂₄H₃₇O₅N₃Si₂Na [MNa⁺]: 526.2169; found: 526.2158.
1-[2- O -Acetyl-6- S -acetyl-3-azido-3-deoxy-6-thio-4- O -(triethylsilanyl)-β- d -altropyranosyl]-2-bromoethyne (23)
[α]_D ^¹8 +5.1 (c 0.3, CHCl₃). IR (CHCl₃ cast): ν_max = 2947, 2110, 1755, 1693 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 4.94 (1 H, dd, J = 3.1, 1.5 Hz), 4.52 (1 H, d, J = 1.4 Hz), 3.87-3.83 (2 H, m), 3.71 (1 H, td, J = 9.2, 2.6 Hz), 3.60 (1 H, dd, J = 13.6, 2.7 Hz), 2.74 (1 H, dd, J = 13.6, 9.5 Hz), 2.33 (3 H, s), 2.16 (3 H, s), 0.99 (9 H, t, J = 8.0 Hz), 0.68-0.62 (6 H, m). ^¹³C NMR (125 MHz, CDCl₃): δ = 195.0 (C), 169.7 (C), 76.0 (CH), 74.2 (C), 71.5 (CH), 70.0 (CH), 65.9 (CH), 61.6 (CH), 47.8 (C), 31.2 (CH₂), 30.5 (CH₃), 20.7 (CH₃), 6.7 (CH₃), 4.8 (CH₂). HRMS-FAB⁺: m/z calcd for C₁₈H₂₉O₅N₃SSi⁷⁹Br [MH⁺]: 506.0781; found: 506.0771.
1-(2,4-Di- O -triethylsilanyl-5- C -vinyl-β-d-glucopyran-osyl)-2-trimethylsilanylethyne (28)
[α]_D ^²² -65.9 (c 0.7, CHCl₃). IR (CHCl₃ cast): ν_max = 3565, 2182, 1729, 1458 cm^-¹. ^¹H NMR (600 MHz, CDCl₃): δ = 6.00 (1 H, dd, J = 18.0, 11.3 Hz), 5.45 (1 H, dd, J = 18.1, 1.4 Hz), 5.43 (1 H, dd, J = 11.2, 1.2 Hz), 4.21 (1 H, d, J = 9.5 Hz), 3.83 (1 H, d, J = 9.8 Hz), 3.56 (1 H, dd, J = 11.7, 11.0 Hz), 3.48 (1 H, dd, J = 9.5, 8.8 Hz), 3.39 (1 H, dd, J = 11.9, 2.9 Hz), 3.36 (1 H, ddd, J = 9.5, 8.9, 3.0 Hz), 2.19 (1 H, dd, J = 10.9, 3.1 Hz), 2.09 (1 H, d, J = 2.9 Hz), 0.99 (18 H, m), 0.71 (12 H, m), 0.20 (9 H, s). ^¹³C NMR (150 MHz, CDCl₃): δ = 132.5 (CH), 119.2 (CH₂), 103.4 (C), 89.9 (C), 81.7 (C), 76.0 (CH), 75.9 (CH), 71.0 (CH), 66.7 (CH), 65.9 (CH₂), 6.9 (CH₃), 5.2 (CH₂), 5.3 (CH₂), 5.1 (CH₂), -0.2 (CH₃). HRMS (CI⁺): m/z calcd for C₂₅H₅₀O₅Si₃ [MH⁺]: 515.3044; found:515.3050.

19

CAUTION: The byproduct of this procedure is the highly explosive hydrazoic acid.

24

1,6-Anhydro-5- C -vinyl-β-d-glucopyranose (27)
Thioanisole (0.17 mL, 2.1 mmol) was added to a stirred solution of glucofuranoside 26 (1.00 g, 2.08 mmol) and TFA (0.05 mL, 0.4 mmol) in 80% aq AcOH (20.8 mL). The mixture was stirred under reflux for 3 d, concentrated in vacuo, and co-evaporated with heptane (3 × 80 mL) to give a viscous black oil. MeOH (40 mL) was added and the organic solution removed from the insoluble residue using a Pasteur pipette. NaOMe (225 mg, 4.16 mmol) was added to the MeOH solution and the mixture stirred for 3 h. The solution was concentrated in vacuo and the residue purified by flash column chromatography (MeOH-CH₂Cl₂ 1:99 → 10:90) to give compound 27 (284 mg, 73%) as a viscous brown oil; [α]_D ^²0 -73.1 (c 1.0, EtOH). IR (neat): ν_max = 3368, 2901, 1646, 1416 cm^-¹. ^¹H NMR (600 MHz, CD₃OD): δ = 6.05 (1 H, dd, J = 17.6, 11.2 Hz), 5.44 (1 H, dd, J = 17.6, 1.3 Hz), 5.44 (1 H, br t, J = 1.6 Hz), 5.31 (1 H, dd, J = 11.2, 1.3 Hz), 4.32 (1 H, d, J = 7.0 Hz), 3.82 (1 H, br q, J = 1.5 Hz), 3.59 (1 H, br s), 3.45 (1 H, br q, J = 1.5 Hz), 3.42 (1 H, d, J = 7.0 Hz). ^¹³C NMR (150 MHz, CD₃OD): δ = 135.0 (CH), 115.1 (CH₂), 103.1 (CH), 82.6 (C), 74.1 (CH), 72.6 (CH), 69.6 (CH), 69.4 (CH₂). HRMS (CI⁺): m/z calcd for C₈H₁₃O₅ [MH⁺]: 189.0763; found: 189.0765.