Diastereoselective Synthesis of the Acyl Side-Chain and Amino Acid (2S,3R)-3-Hydroxy-3-Methylproline Fragments of Polyoxypeptin A

Zhiyong Chen; Tao Ye

doi:10.1055/s-2005-918924

LETTER

Diastereoselective Synthesis of the Acyl Side-Chain and Amino Acid (2S,3R)-3-Hydroxy-3-Methylproline Fragments of Polyoxypeptin A

Zhiyong Chen^a, Tao Ye*^a,b
^a Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China
^b Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery & Synthesis and Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, P. R. of China
Fax: +852 22641912; e-Mail: bctaoye@inet.polyu.edu.hk;

Abstract

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Abstract

Synthesis of the acyl side-chain and amino acid (2S,3R)-3-hydroxy-3-methylproline units of the potent depsipeptide polyoxypeptin A, is described. Key intermediates were secured via diastereoselective addition involving a homoenolate ion and allylation of an aminoketone, respectively.

Key words

asymmetric aldol - asymmetric dihydroxylation - polyoxypeptin A - homoenolate - ketone allylation - amino acids

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References

<A NAME="RW01405ST-1A">1a</A> Umezawa K. Nakazawa K. Uemura T. Ikeda Y. Kondo S. Naganawa H. Kinoshita N. Hashizume H. Hamada M. Takeuchi T. Ohba S. Tetrahedron Lett. 1998, 39: 1389

<A NAME="RW01405ST-1B">1b</A> Umezawa K. Nakazawa K. Ikeda Y. Naganawa H. Kondo S. J. Org. Chem. 1999, 64: 3034

<A NAME="RW01405ST-2A">2a</A> Noguchi Y. Yamada T. Uchiro H. Kobayashi S. Tetrahedron Lett. 2000, 41: 7499

<A NAME="RW01405ST-2B">2b</A> Lorca M. Kurosu M. Tetrahedron Lett. 2001, 42: 2431

<A NAME="RW01405ST-2C">2c</A> Makino K. Suzuki T. Awane S. Hara O. Hamada Y. Tetrahedron Lett. 2002, 43: 9391

<A NAME="RW01405ST-2D">2d</A> Qin DG. Yao ZJ. Tetrahedron Lett. 2003, 44: 571

<A NAME="RW01405ST-3A">3a</A> Qin DG. Zha HY. Yao ZJ. J. Org. Chem. 2002, 67: 1038

<A NAME="RW01405ST-3B">3b</A> Noguchi Y. Uchiro H. Yamada T. Kobayashi S. Tetrahedron Lett. 2001, 42: 5253

<A NAME="RW01405ST-3C">3c</A> Bialer M, Yagen B, Spiegelstein O, Roeder M, and Schurig V. inventors; PCT Int. Appl., WO 9830536 A1 19980716.

<A NAME="RW01405ST-3D">3d</A> Makino K. Kondoh A. Hamada Y. Tetrahedron Lett. 2002, 43: 4695

<A NAME="RW01405ST-3E">3e</A> Shen JW. Qin DG. Zhang HW. Yao ZJ. J. Org. Chem. 2003, 68: 7479

<A NAME="RW01405ST-3F">3f</A> Makino K. Suzuki T. Hamada Y. Bull. Chem. Soc. Jpn. 2004, 77: 1649

<A NAME="RW01405ST-3G">3g</A> Suzuki T. Makino K. Hamada Y. Peptide Sci. 2004, 40: 57

<A NAME="RW01405ST-3H">3h</A> Davis FA. Ramachandar T. Liu H. Org. Lett. 2004, 6: 3393

<A NAME="RW01405ST-3I">3i</A> Merino P. Revuelta J. Tejero T. Cicchi S. Goti A. Eur. J. Org. Chem. 2004, 776

<A NAME="RW01405ST-3J">3j</A> Haddad M. Larchevêque M. Tetrahedron: Asymmetry 2005, 16: 2243

<A NAME="RW01405ST-4A">4a</A> Dess DB. Martin JC. J. Am. Chem. Soc. 1991, 113: 7277

<A NAME="RW01405ST-4B">4b</A> Stevenson PJ. Treacy AB. Nieuwenhuyzen M. J. Chem. Soc., Perkin Trans. 2 1997, 589

<A NAME="RW01405ST-5A">5a</A> Whisler MC. Vaillancourt L. Beak P. Org. Lett. 2000, 2: 2655

<A NAME="RW01405ST-5B">5b</A> Pippel DJ. Weisenburger GA. Faibish NC. Beak P. J. Am. Chem. Soc. 2001, 123: 4919

<A NAME="RW01405ST-5C">5c</A> Whisler MC. Beak P. J. Org. Chem. 2003, 68: 1207

Procedure for the Synthesis of Enamine 10.
(-)-Sparteine (773 mg, 3.3 mmol) and n-BuLi (2.1 mL, 1.6 M in hexane) in toluene (20 mL) were cooled to -78 °C under nitrogen and pre-cooled 9 (0.784 g, 2.35 mmol) in toluene (15 mL) was added. The bright yellow mixture was stirred for 45 min and Et₂AlCl (3.5 mL, 1 M in hexane) was added, and the color faded to pale yellow. After 1 h, propionaldehyde (1.5 mL, 20.8 mmol) was added and the mixture was stirred for 12 h at this temperature. Then, MeOH (20 mL) was added and the reaction warmed to r.t. After warming to r.t., HCl (20 mL, 1 M) was added and the mixture extracted with EtOAc (2 × 50 mL). The organic extracts were washed with brine (20 mL), dried (Na₂SO₄), concentrated and purified by flash chromatography.

<A NAME="RW01405ST-7">7</A> Sharpless KB. Amberg W. Bennani YL. Crispino GA. Hartung J. Jeong KS. Kwong HL. Morikawa K. Wang ZM. Xu DQ. Zhang XL. J. Org. Chem. 1992, 57: 2768

Compound 17: ¹H NMR (300 MHz, CDCl₃): δ = 0.72 (3 H, d, J = 6.8 Hz), 0.73 (3 H, q, J = 6.8 Hz, 8.2 Hz), 0.80 (3 H, t, J = 7.4 Hz), 0.93 (2 H, m), 1.10 (1 H, m), 1.11 (1 H, m), 1.17 (1 H, m), 1.22 (1 H, m), 1.24 (3 H, t, J = 7.1 Hz), 1.32 (1 H, m), 1.35 (1 H, m), 1.50 (3 H, s), 1.52 (1 H, m), 1.63 (1 H, m), 1.69 (1 H, m), 1.85 (1 H, m), 3.40 (1 H, m), 3.56 (1 H, d, J = 2.5 Hz), 3.61 (1 H, s), 4.19 (2 H, q, J = 7.1 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 173.59, 96.78, 79.40, 75.68, 61.83, 38.25, 35.82, 31.04, 31.02, 28.47, 25.16, 24.64, 19.14, 18.64, 14.23, 11.60, 8.81. [α]_D ²⁰ +20.4 (c 0.6, CHCl₃). HRMS: m/z calcd for C₆H₁₁NO₃ [M - H₂O]: 298.2144; found: 298.2151.

<A NAME="RW01405ST-9A">9a</A> Wagner I. Musso H. Angew. Chem., Int. Ed. Engl. 1983, 22: 816

<A NAME="RW01405ST-9B">9b</A> Williams RW. Synthesis of Optically Active α-Amino Acids Pergamon Press; New York: 1989.

<A NAME="RW01405ST-9C">9c</A> Duthaler RO. Tetrahedron 1994, 50: 1539

<A NAME="RW01405ST-9D">9d</A> Davies JS. Amino Acids, Peptides and Proteins Vol. 1-31: Royal Society of Chemistry; Cambridge: 1968-2000.

<A NAME="RW01405ST-10">10</A> Yamazaki M. Okuyama E. Tetrahedron Lett. 1981, 22: 135

<A NAME="RW01405ST-11A">11a</A> Williams RM. Cao J. Tsujishima H. Angew. Chem. Int. Ed. 2000, 39: 2540

<A NAME="RW01405ST-11B">11b</A> Lee BH. Clothier MF. J. Org. Chem. 1997, 62: 1795

<A NAME="RW01405ST-12A">12a</A> Dias LC. Meira PRR. Synlett 2000, 37

<A NAME="RW01405ST-12B">12b</A> Hertweck C. Boland W. J. Org. Chem. 1999, 64: 4426

<A NAME="RW01405ST-12C">12c</A> Hanessian S. Park H. Yang RY. Synlett 1997, 351

<A NAME="RW01405ST-12D">12d</A> Cokley TM. Isaacs NS. McCluskey A. Young DJ. Main Group Met. Chem. 1997, 20: 581

<A NAME="RW01405ST-12E">12e</A> Dinh TQ. Du XH. Armstrong RW. J. Org. Chem. 1996, 61: 6606

<A NAME="RW01405ST-12F">12f</A> Roush WR. Hunt JA. J. Org. Chem. 1995, 60: 798

<A NAME="RW01405ST-12G">12g</A> Nicolaou KC. Koide K. Bunnage ME. Chem. Eur. J. 1995, 1: 454

<A NAME="RW01405ST-12H">12h</A> Ciapetti P. Taddei M. Ulivi P. Tetrahedron Lett. 1994, 35: 3183

<A NAME="RW01405ST-12I">12i</A> Barrett AGM. Edmunds J. Hendrix JA. Malecha JW. Parkinson CJ. J. Chem. Soc., Chem. Commun. 1992, 1240

<A NAME="RW01405ST-12J">12j</A> Barrett AGM. Malecha JW. J. Org. Chem. 1991, 56: 5243

<A NAME="RW01405ST-12K">12k</A> Vara Prasad JVN. Rich DH. Tetrahedron Lett. 1990, 31: 1803

<A NAME="RW01405ST-13">13</A> Pace RD. Kabalka GW. J. Org. Chem. 1995, 60: 4838

The diastereomeric excess of amino alcohols 24a and 24b were determined by chiral HPLC analysis (conditions: column: Daicel OD; mobile phase: hexane-i-PrOH = 9:1; detection UV: 254 nm; flow rate: 1 mL/min; t _R(min): 5.06 (24a, syn isomer), 3.58 (24a, anti isomer); 27.00 (24b, syn isomer), 19.66 (24b, anti isomer).

<A NAME="RW01405ST-15">15</A> Brown HC. Ramachandran PV. Pure Appl. Chem. 1994, 66: 201 ; and references cited therein

Procedure for the Synthesis of 24a.
Allylmagnesium bromide (1 M solution in Et₂O, 5 mL) was added dropwise to a well-stirred solution of (+)-B-methoxy-diisopinocampheylborane (5 mmol in 30 mL Et₂O) at 0 °C. Following completion of addition, the reaction mixture was vigorously stirred for 1 h at 25 °C. The solution was removed under vacuum and the residue was extracted with anhyd pentane. Evaporation of pentane gave the (Ipc)₂BAll which was used in the next step. Aminoketone 21a (4 mmol in 10 mL CH₂Cl₂) was added into the Ipc₂BAll solution (in 40 mL anhyd Et₂O) at 25 °C and then stirred overnight. The reaction was quenched with MeOH and treated with Et₃N (1.39 mL) and 30% H₂O₂ (10 mmol, 0.68 mL). Standard work-up and purification of the resulting crude product by chromatography on silica gel gave the corresponding homo-allylic alcohol 24a in 96% yield.

Compound 20a: ¹H NMR (300 MHz, CDCl₃): δ = 0.63 (6 H, q, J = 7.6 Hz), 0.99 (9 H, t, J = 7.9 Hz), 1.37 (9 H, s), 1.57 (3 H, m), 2.14-2.29 (2 H, m), 3.96-4.04 (1 H, m), 4.31 (1 H, t, J = 10.7 Hz), 4.50-4.84 (2 H, m), 5.13 (2 H, m), 5.80 (1 H, m), 7.40 (2 H, t, J = 7.2 Hz), 7.53 (1 H, t, J = 8.0 Hz), 8.05 (2 H, t, J = 8.0 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 166.7, 155.3, 133.3, 132.8, 130.1, 129.8, 128.2, 118.9, 79.1, 64.5, 55.4, 46.2, 28.3, 25.1, 7.1, 6.7. [α]_D ²⁰ +15.4 (c 10.0, CHCl₃).

<A NAME="RW01405ST-18">18</A> Zhong YL. Shing TKM. J. Org. Chem. 1997, 62: 2622

<A NAME="RW01405ST-19">19</A> Carlsen PHJ. Katsuki T. Martin VS. Sharpless KB. J. Org. Chem. 1981, 46: 3936

Compound 28: ¹H NMR (300 MHz, CDCl₃): δ = 3.73 (3 H, s), 3.48 (1 H, s), 3.22-3.27 (1 H, m), 2.97-2.90 (1 H, m), 2.50 (1 H, br s), 1.96-1.76 (2 H, m), 1.56 (3 H, s), 0.93 (9 H, t, J = 7.8 Hz), 0.57 (6 H, q, J = 7.8 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 171.62, 82.61, 71.90, 51.62, 44.86, 42.17, 25.94, 6.86, 6.36.

<A NAME="RW01405ST-21">21</A> Zanardi F. Battistini L. Nespi M. Rassu G. Spanu P. Cornia M. Casiraghi G. Tetrahedron: Asymmetry 1996, 7: 1167

Compound 19: ¹H NMR (500 MHz, D₂O): δ = 3.86 (1 H, s), 3.54 (1 H, ddd), 3.45 (1 H, ddd), 2.15 (2 H, m), 1.60 (3 H, s). ¹³C NMR (125 MHz, D₂O): δ = 171.16, 78.81, 70.06, 43.69, 39.82, 24.22. HRMS: m/z calcd for C₆H₁₁NO₃: 145.0738; found: 145.0715. [α]_D ²⁰ - 41 (c 0.3, H₂O).