Synthesis of Phenol and Benzoquinone derivatives from New Zealand Brown Alga Perithalia capillaris

A proposal submitted to the Faculty

Of

Drexel University

By

Khalid Baig Mirza

In partial fulfillment of the requirements

for the degree of

Doctor of Philosophy

1.Introduction

A bis-prenylated benzoquinone isolated from theNew Zealand brown alga Perithalia capillaris was recently reported[1] by Perry, Sansom, Larsen, et.al. Invitro studies indicated that this compound inhibited the superoxide production by human neutrophils (IC502.1μM). It was also highly potent at inhibiting the proliferation of HL60 cells (IC50 0.34 μM). Six other prenylated quinones and phenols along with a thaizone derivative were isolated.

Commonly used non steroidal anti-inflammatory drugs (NSAIDS) target cyclooxygenase and phospholipase enzymes in the cascade of reactions leading to an inflammation. Certain diseases including gouty arthritis and non-atopic asthma are a result of Superoxide production by neutrophils[2]. Superoxide inhibition has therefore been a main area of research.

HL60 cell line once isolated from a patient with acute myeloid leukemia resembles promyleocytes. These cells can be made to differentiate terminally in vitro to granulocyte-like and monocyte / macrophage-like cells. The interesting fact about these cells is that the c-myc proto-oncogene and c-myc mRNA levels decline rapidly once differentiation is induced.[3]

This work intends to proposea short and viable synthesis for each of the eight natural products reportedly isolated from Perithalia capillaris[4]. The structures of these compounds are as listed below;

[5],[6],[7]

[8],[9] [10],[11]

Compound 3a may also be prepared by a simple condensation reaction of hydroquinone in THF at 65-70 C with isoprene in heptane; the reaction is catalyzed by Amberlyst-15 resin [12]. 3a may then be subjected to Friedel Crafts alkylation using prenylbromide and a lewis acid to obtain compound 3.

[13],[14],[15]

Compound 4a after removal of the nitro group can be converted to the product by a [1, 3] sigmatropic rearrangement of the prenyl derivative catalyzed by Florisil, [16]

[17],[18],[19][20],[21],[22][23],[24],[25][26].

The compounds canbe extracted from methylene chloride and water, dried over anhydrous MgSO4 or anhydrous CaCl2, further dried in a vacuum dessicator. The compounds can be analyzed using various NMR techniques. The results must be compared to the published data for a confirmation of the structural identity of the compounds.

CONCLUSION:

In conclusion, a simple synthesis has been proposed for the compounds. They can thus be easily synthesized on large scale.

REFERENCES:

Sansom, Larsen, Perry et.al J. Nat. Prod.,70 (12);

2Brent R.Copp et.al J. Nat. Prod. 2007, 70, 936-940;

3Br J Cancer Suppl. 1988 Dec; 9:41-5.

4 Sansom, Larsen, Perry et.al J. Nat. Prod.,70 (12);

5 Name reactions and Reagents in Organic Synthesis, Bradford, et.al. 2005, 156-157

6 Mehta and Pan; Org. Lett. 2004 Vol 6, No. 5 811-813

7 Solomons, Fryhle; Organic Chemistry; 9/e 2007; John Wiley & Sons, Inc.

8 Mehta and Pan; Org. Lett. 2004 Vol 6, No. 5 811-813

9 Solomons, Fryhle; Organic Chemistry; 9/e 2007; John Wiley & Sons, Inc.

10Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, (7), 1525-9; 1987

11Sato,Miyamoto, et.al; J. Org. Chem.; 1987;52(24) pp 5495-5497;

12Banerji, Jain and Kalena; Molecules 1997, 2, 100–105

13Mehta and Pan; Org. Lett. 2004 Vol 6, No. 5 811-813

14Solomons, Fryhle; Organic Chemistry; 9/e 2007; John Wiley & Sons, Inc.

15Chung and KimJ. Am. Chem. Soc. 2001, 123, 11071-11072

16Talams, Smith, et.al; Tett. Lett.1997, 38, 4725

17Sato,Miyamoto, et.al; J. Org. Chem.; 1987;52(24) pp 5495-5497;

18Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, (7), 1525-9; 1987

19Solomons, Fryhle; Organic Chemistry; 9/e 2007; John Wiley & Sons, Inc.

20Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, (7), 1525-9; 1987

21Sato,Miyamoto, et.al; J. Org. Chem.; 1987;52(24) pp 5495-5497;

22Solomons, Fryhle; Organic Chemistry; 9/e 2007; John Wiley & Sons, Inc.

23Tzeng, Lee, Chen, Wang Tetrahedron Letters Volume 37, Issue 35, 26 August 1996, Pages 6369-6370;

24Copp, Brent, et.al. J. Nat. Prod.2007, 70, 936-940;

25Mehta and Pan; Org. Lett. 2004 Vol 6, No. 5 811-813

26Solomons, Fryhle; Organic Chemistry; 9/e 2007; John Wiley & Sons, Inc.

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