Follow my blog with Bloglovin

One-Pot Synthesis of Alkyl Styryl Sulfides Free from Transition Metal/Ligand Catalyst and Thiols http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201201163/abstract

European Journal of Organic Chemistry

Early View (Online Version of Record published before inclusion in an issue) Adrián A. Heredia and Alicia B. Peñéñory Article first published online: 19 DEC 2012 | DOI: 10.1002/ejoc.201201163 They have developed a one-pot methodology for the synthesis of alkyl arylvinyl sulfides in good to excellent yields, free of any metal/ligand systems and from malodorous and air-sensitive alkyl thiols. This procedure uses commercially available potassium thioacetate, low temperatures, and short reaction times.

abstract A new protocol for the one-pot synthesis of styryl alkyl sulfides was developed. This methodology involves the in situ generation of thiolate anions by nucleophilic substitution between potassium thioacetate and alkyl halides followed by fragmentation. Further reactions of these thiolate anions with substituted (E,Z)-β-styryl halides gave the corresponding sulfides with retention of stereochemistry in good to excellent yields. This procedure does not require a metal catalyst, it proceeds under mild conditions and in short times, and it is free from malodorous and air-sensitive alkyl thiols.   THANKS AND REGARD'S DR ANTHONY MELVIN CRASTO Ph.D  amcrasto@gmail.com MOBILE-+91 9323115463 GLENMARK SCIENTIST , NAVIMUMBAI, INDIA web link http://anthonycrasto.jimdo.com/ http://www.anthonymelvincrasto.yolasite.com/  http://www.slidestaxx.com/anthony-melvin-crasto-phd  https://sites.google.com/site/anthonycrastoorganicchemistry/sites---my-own-on-the-net  http://anthonycrasto.wordpress.com/  http://organicchemistrysite.blogspot.com/  http://www.mendeley.com/profiles/anthony-melvin-crasto/ Congratulations! Your presentation titled "Anthony Crasto Glenmark scientist, helping millions with websites" has just crossed MILLION views.  アンソニー 安东尼 Энтони 안토니 أنتوني  join my process development group on google http://groups.google.com/group/organic-process-development  http://www.epernicus.com/amc10  http://scipeople.com/users/87574341/  https://sites.google.com/site/amcrasto/  http://amcrasto.mixxt.com 

The Formal Total Synthesis of FR252921 – An Immunosuppressant European Journal of Organic Chemistry Volume 2013, Issue 2, pages 376–388, January 2013 J. S. Yadav and Sandip Sengupta Article first published online: 15 NOV 2012 | DOI: 10.1002/ejoc.201201097 http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201201097/abstract   The formal total synthesis of FR252921 is described. The key steps include the preparation of three fragments starting from 1,4-butanediol, (R)-malic acid, and prenol, respectively, followed by two consecutive peptide couplings of the three fragments. Abstract The formal total synthesis of FR252921 is described. The key steps include the preparation of three fragments starting from 1,4-butanediol, (R)-malic acid, and prenol, respectively, followed by two consecutive peptide couplings of the three fragments. Other key steps involve an allene-type rearrangement or enyne isomerization to install the triene moiety, a Seebach methylation, a Julia olefination to construct the trisubstituted diene unit, and an enzymatic resolution strategy to generate the C-18 stereocenter. other articles of relevance

FR252921, a novel immunosuppressive agent isolated from Pseudomonas fluorescens no. 408813 II. In vitro property and mode of action.

Abstract

A novel immunosuppressive agent, FR252921 was isolated from the cultured broth of a species of Pseudomonas fluorescens. We have shown that FR252921 inhibited splenic proliferation stimulated with LPS, insensitive to calcinuerin inhibitor. In this study, FR252921 was found to inhibit IL-2 and IL-12 production as well as proliferaion of splenocyte. Analysis of transcription activity revealed that FR252921 inhibited activating protein-1 (AP-1). Exposures of antigen presenting cells (APC) to FR252921 attenuated proliferation supplemented by naïve T cells. Further, FR252921 strongly suppressed splenic dendritic cell proliferation stimulated with LPS and anti-CD40 mAb, while it did not inhibit purified T cell activation, including CD154 expression and IL-2 production. These results suggest that APC is dominant target cell population.

Chemistry. 2009;15(14):3457-73. doi: 10.1002/chem.200802649.

Synthesis of two bioactive natural products: FR252921 and pseudotrienic acid B.

Amans D, Bellosta V, Cossy J.

Source

Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS, 10 rue Vauquelin, 75231 Paris, France.

Abstract

Concise and highly convergent syntheses of the immunosuppressive agent FR252921 and the related antimicrobial natural product pseudotrienic acid B were achieved from a common intermediate by using optically active titanium complexes to control the configuration of the stereogenic centers, a highly stereo- and regioselective cross-metathesis to generate the triene moieties, and a Stille cross-coupling to install the dienic units.

Synthesis of a Promising Immunosuppressant:  FR252921

Dominique Amans , Véronique Bellosta , and Janine Cossy

Laboratoire de Chimie Organique, ESPCI, CNRS, 10 rue Vauquelin, 75231 Paris Cedex 05, France

Org. Lett., 2007, 9 (23), pp 4761–4764

DOI: 10.1021/ol702110k

http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201201097/abstract    

The α-tocopherol form of vitamin E Vitamin E refers to a group of eight fat-soluble compounds that include both tocopherolsand tocotrienols.^[1] There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet.^[2] γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings.^[3][4] In the North American diet, α-Tocopherol, the most biologically active form of vitamin E, is the second most common form of vitamin E. This variant of vitamin E can be found most abundantly in wheat germ oil, sunflower, and safflower oils.^[4][5] It is a fat-soluble antioxidant that stops the production of reactive oxygen species formed when fat undergoes oxidation.^[6][7][8]

• Synthesis of Vitamin E

Vitamin E (CAS NO.: 59-02-9), with other names as 2(R),5,7,8-Tetramethyl-2-[4(R),8(R),12-trimethyltridecyl]-3,4-dihydro-2H-1-benzopyran-6-ol, could be produced through the following synthetic routes.,

 

           

 References

1. Brigelius-Flohe, B; Traber (1999). "Vitamin E: function and metabolism". FASEB 13: 1145–1155.
2. Traber, MG (1998). "The biological activity of vitamin E". The Linus Pauling Institute. Retrieved 6 March 2011.
3. Bieri, JG; Evarts (1974). "γ-Tocopherol: metabolism, biological activity and significance in human vitamin E nutrition". American Journal of Clinical Nutrition 27 (9): 980–986. PMID 4472121.
4. Brigelius-Flohé R, Traber MG (1 July 1999). "Vitamin E: function and metabolism". FASEB J. 13 (10): 1145–55. PMID 10385606.
5. Reboul E, Richelle M, Perrot E, Desmoulins-Malezet C, Pirisi V, Borel P (15 November 2006). "Bioaccessibility of carotenoids and vitamin E from their main dietary sources". Journal of Agricultural and Food Chemistry 54 (23): 8749–8755. doi:10.1021/jf061818s.PMID 17090117.
6. National Institute of Health (4 May 2009). "Vitamin E fact sheet".
7. Herrera; Barbas, C (2001). "Vitamin E: action, metabolism and perspectives". Journal of Physiology and Biochemistry 57 (2): 43–56.doi:10.1007/BF03179812. PMID 11579997.
8. Packer L, Weber SU, Rimbach G (2001). "Molecular aspects of α-tocotrienol antioxidant action and cell signalling". Journal of Nutrition 131 (2): 369S–73S. PMID 11160563.

• Vitamin E bound to proteins in the PDB
• Vitamin E Medline Plus, Medical Encyclopedia, U.S. National Library of Medicine
• Vitamin E Office of Dietary Supplements, National Institutes of Health
• Jane Higdon, "Vitamin E", Micronutrient Information Center, Linus Pauling Institute, Oregon State University
• Vitamin E Food Charts

The Bingel reaction in fullerene chemistry is a fullerene cyclopropanation reaction to a methanofullerenefirst discovered by C. Bingel in 1993 with the bromo derivative of diethyl malonate in the presence of a basesuch as sodium hydride or DBU.^[1] The preferred double bonds for this reaction on the fullerene surface are the shorter bonds at the junctions of two hexagons (6-6 bonds) and the driving force is relief of steric strain.

The reaction is of importance in the field of chemistry because it allows the introduction of useful extensions to the fullerene sphere. These extensions alter their properties for instance solubility and electrochemical behavior and therefore widen the range of potential technical applications.

Reaction mechanism

The reaction mechanism for this reaction is as follows: a base abstracts the acidic malonate proton generating a carbanion or enolatewhich reacts with the electron deficient fullerene double bond in a nucleophilic addition. This in turn generates a carbanion which displaces bromine in a nucleophilic aliphatic substitution in an intramolecular ring cyclopropane ring closure.

Scope

The Bingel reaction is a popular method in fullerene chemistry. The malonate (functionalized with the halide atom) is often obtained in situ in a mixture of base and tetrachloromethane or iodine.^[2] The reaction is also known to take place with the ester groups replaced byalkyne groups in dialkynylmethanofullerenes.^[2]

Bingel reaction of fullerene with a malonate ester and a) sodium hydride or DBUin toluene at room temperature 45% yield.

An alternative to the Bingel reaction is a fullerene diazomethane reaction. N-(Diphenylmethylene)glycinate Esters ^[3] in a Bingel reaction take a different conjugate course and react to a fullerene dihydropyrrole.

Bingel reaction with N-(Diphenylmethylene)glycinate Ester

Retro-Bingel reaction

Protocols exist for the removal of the methano group based, on electrolytic reduction ^[4][5] or amalgamated magnesium ^[6]

References

Substituted indole derivatives for the treatment of immunological disorders,WO 2012156936, Novartis AG, Protein kinase C theta inhibitor

TITLE-Substituted indole derivatives for the treatment of immunological disorders

Protein kinase C theta inhibitor

WO 2012156936, 22.11.2012, Novartis AG

GENERAL STRUCTURE

DESCRIBED IS

Phosphoric acid mono-[3-[3-(4,7-diaza-spiro[2.5]oct-7-yl)-isoquinolin-1 -yl]-4-(7-methyl-1 H-indol-3-yl)-2,5-dioxo-2,5-dihydro-pyrrol-1 -ylmethyl] ester

¹H-NMR (400 MHz, DMSO-d6): 12.10 (s, 1 H), 8.08 (d, 1 H), 7.65-7.61 (m, 2H), 7.44 (f, 1 H), 7.20 (s, 1 H), 7.06 (f, 1 H), 6.74 (d, 1 H), 6.43 (f, 1 H), 6.00 (d, 1 H), 5.29 (d, 2H), 3.87-3.01 (m, 6H), 2.37 (s, 3H), 0.97-0.62 (m, 4H).

³¹P-NMR (162 MHz, DMSO-d6): -6.0.

LCMS: [M+1]⁺ = 574.0, Rt ⁽¹⁾ = 1.77 min., Rt ⁽²⁾ = 0.71 min.

Descibed is a  crystalline form of phosphoric acid mono-[3-[3-(4,7-diaza-spiro[2.5]oct-7-yl)-isoquinolin-1- yl]-4-(7-methyl-1 H-indol-3-yl)-2,5-dioxo-2,5-dihydro-pyrrol-1-ylmethyl] ester, especially the mono-hydrate, which preferably has an X-ray powder diffraction pattern with at least one, preferably two, more preferably three, even more preferably four, especially five, most preferably all of the following peaks at an angle of refraction 2 theta (Θ) of 9.525, 16.356, 17.091 , 18.005, 20.859, each ± 0.2

Jasmone is a natural organic compound extracted from the volatile portion of the oil fromjasmine flowers. It is a colorless to pale yellow liquid that has the odor of jasmine. Jasmone can exist in two isomeric forms with differing geometry around the pentenyl double bond, cis-jasmone and trans-jasmone. The natural extract contains only the cis form, while synthetic material is often a mixture containing both forms, with the cis form predominating. Both forms have similar odors and chemical properties.

Jasmone is produced within plants by the metabolism of jasmonate, from linolenic acid by the octadecanoid pathway. It can act as either an attractant or a repellent for various insects. Commercially jasmone is used primarily in perfumes and cosmetics.

An attempt to make Z jasmone – an important constituent of many perfumes

In fact one synthesis uses the following as carbon sources:

cis (Z) jasmone ,

cas no 488-10-8, 3-methyl-2-[(2Z)-pent-2-en-1-yl]cyclopent-2-en-1-one

ref-(Can. J. Chem. 1978, Vol 56, p2301)

1    W. Theilheimer. Synthetic Methods of Organic Chemistry. Volume 31, 1977, p. 352
2   Tetrahedron, 39 (24), p. 4127, 1983

• Thomas Koch, Katja Bandemer, Wilhelm Boland (1997). "Biosynthesis of cis-Jasmone: a pathway for the inactivation and the disposal of the plant stress hormone jasmonic acid to the gas phase?". Helvetica Chimica Acta 80 (3): 838–850.doi:10.1002/hlca.19970800318.
• L. Ruzicka, M. Pfeiffer (1933). "Über Jasminriechstoffe I. Die Konstitution des Jasmons". Helvetica Chimica Acta 16: 1208–1214. doi:10.1002/hlca.193301601153.

Predict NMR spectrum

WO 2012130821, BENZOIC ACID SALT OF OTAMIXABAN (SANOFI)

Otamixaban (INN) is a direct factor Xa inhibitor,^[1] currently being developed by the French pharmaceutical company Sanofi-Aventis as a treatment for acute coronary syndrome.

Methyl (2R,3R)-2-{3-[amino(imino)methyl]benzyl}-3-{[4-(1-oxidopyridin-4-yl)benzoyl]amino}butanoate

Guertin KR, Choi YM (2007). “The discovery of the Factor Xa inhibitor otamixaban: from lead identification to clinical development”.  

Curr. Med. Chem. 14 (23): 2471–81.doi:10.2174/092986707782023659. PMID 17979700.

Methyl (2R,3R)-2-{3-[amino(imino)methyl]benzyl}-3-{[4-(1 -oxidopyridin-4-yl)benzoyl]amino}butanoate, (CAS number 193153-04-7) has the International Nonproprietary Name Otamixaban

The present invention (WO2012130821) 4TH OCT 2012, BENZOIC ACID SALT OF OTAMIXABAN, SANOFI relates to a benzoic acid salt of methyl (2R,3R)-2-{3-[amino(imino)methyl]benzyl}-3-{[4-(1 -oxidopyridin-4-yl)benzoyl]amino}butanoate, and to a benzoic acid salt of methyl (2R,3R)-2-{3-[amino(imino)methyl]benzyl}-3-{[4-(1 -oxidopyridin-4-yl)benzoyl]amino}butanoate which is in a crystalline form or in at least partially crystalline form, as well as a process for the preparation of the same, methods of using such salt to treat subjects suffering from conditions which can be ameliorated by the administration of an inhibitor of Factor Xa and shows the structure illustrated in Formula I:

The benzoic acid salt of methyl (2R,3R)-2-{3-[amino(imino)methyl]benzyl}-3-{[4-(1 -oxidopyridin-4-yl)benzoyl]amino}butanoate according to claims 1 to 5 for use in the treatment of acute myocardial infarction, non-ST elevation myocardial infarction, unstable angina, thromboembolism, acute vessel closure associated with thrombolytic therapy, percutaneous transluminal coronary angioplasty, transient ischemic attacks, stroke, intermittent claudication, and restenosis.

http://patentscope.wipo.int/search/en/detail.jsf?docId=WO2012130821&recNum=1&docAn=EP2012055364&queryString=WO:2012130821%20&maxRec=1

COPY PASTE LINK

Green Chemistry Letters and Reviews

Volume 5, Issue 4, 2012

http://www.tandfonline.com/doi/full/10.1080/17518253.2012.687776

DOI:

10.1080/17518253.2012.687776

Sayan Dutta Gupta et al

pages 609-620

synthesis of pyrrole derivative from amino gp,

MAKES ORG CHEM, GOOD RESEARCH PROJECT

Paal-Knorr reaction of aniline and 2,5-diketone; 1-Phenyl-2,5-Dimethylpyrrole

Procedure

Thiemann, F.; Piehler, T.; Haase, D.; Saak, W.; Lützen A. Eur. J. Org. Chem. 2005, 1991.

Preparation of carbon nanotubes as pure substances could benefit from a new way to make gram amounts of “nanohoops” (Chem. Sci., DOI:10.1039/c2sc20719b).

Nanohoops—or cycloparaphenylenes (CPPs)—are like bracelets made from para-linked benzene rings. Stacking of CPPs could be the basis for preparing useful quantities of pure carbon nanotubes.

Synthetic organic chemist Ramesh Jasti—then in Carolyn R. Bertozzi’s group at Lawrence Berkeley National Laboratory’s Molecular Foundry—and coworkers first synthesized CPPs catalytically in 2008

  J. Am. Chem. Soc., DOI: 10.1021/ja807126u).

But the catalysts they used weren’t ideal, and yields of CPPs were low. CPPs have remained so difficult to make that they are currently sold commercially for about $100 per milligram.

Carbon nanotubes (CNTs) have attracted considerable interest due to their unique structure and remarkable properties. Racemic drugs normally contain only one enantiomer that is active, and to get enantiomerically pure drugs to the market is always an urgent task. As promising reagents, chiral selector modified CNTs have been successfully used to separate enantiomers.

Jingang Yu and colleagues, Central South University, China, proposed a novel method to functionalize multi-walled carbon nanotubes (MWCNTs) with hydroxypropyl-β-cyclodextrin (HP-β-CD). These modified multi-walled nanotube samples were fully characterized.

MWCNT-HP-β-CD was used as thin-layer chromatography stationary phase additive to separate clenbuterol enantiomers with satisfactory results. The presence of CNTs permits a higher recognition of enantiomers, so chiral selector modified CNTs have a promising application in resolution of chiral molecules.

Preparation of Hydroxypropyl-β-cyclodextrin Cross-linked Multi-walled Carbon Nanotubes and Their Application in Enantioseparation of Clenbuterol
J. Yu, D. Huang, K. Huang, Y. Hong,
Chinese J. Chem. 2011, 29(5), 893—897.
DOI: 10.1002/cjoc.201190185

Chiral Separation by a Pseudo Membrane in a Triple-Laminar Flow with a Microfluidic Contactor
T.-H. Yoon, L.-Y. Hong, D.-P. Kim,
Chem. Asian J. 2011.
DOI: 10.1002/asia.201000798

The pharmacological activity of ibuprofen, a common painkiller and anti-inflammatory drug, arises predominantly from its (S)-form. Separation of the (R)- and (S)-forms is difficult as they differ only in optical polarity.

The continuous and simultaneous reaction/separation of ibuprofen racemate has been reported by Dong-Pyo Kim and co-workers, Chungnam National University, South Korea. They use an inorganic polymer-chip device with triple-laminar flow. A feed phase withCandida rugosa lipase was used to facilitate esterification of (S)-ibuprofen due to its selective chiral recoginition and resolution. The (S)-ibuprofen ester was then transported through an ionic liquid which acted as a pseudo-membrane. Finally, conversion into (S)-ibuprofen was achieved by H₂SO₄ acid hydrolysis in a receiving stream.

The separated ibuprofen revealed very high chiral purity, with 99.9 % enantiomeric excess throughout the process conditions

One-step conversion of unprotected sugars to -glycosyl azides using 2-chloroimidazolinium salt in aqueous solution
Tomonari Tanaka, Hikaru Nagai, Masato Noguchi, Atsushi Kobayashi and Shin-ichiro Shoda,  Chem. Commun., 2009, 3378
DOI: 10.1039/b905761g

http://pubs.rsc.org/en/Content/ArticleLanding/2009/CC/b905761g

Various -glycosyl azides have been synthesized directly in water by the reaction of unprotected sugars and sodium azide mediated by 2-chloro-1,3-dimethylimidazolinium chloride.

Carbohydrate chemistry in drug discovery

M. Carmen Galan ,  David Benito-Alifonso and Gregory M. Watt

Affiliation Information 

1. School of Chemistry,University of Bristol,Cantock's Close, Bristol, U.K

Org. Biomol. Chem., 2011, 9, 3598-3610

DOI:10.1039/C0OB01017K

The multitude of roles that carbohydrates and their glyco-conjugates play in biological processes has stimulated great interest in determining the nature of their interactions in both normal and diseased states.

http://www.slideshare.net/anthonycrasto64/anthony-crasto-buckyball is my presentation on slideshare, please click link for a view

Buckminsterfullerene or Buckyball

READ AT

http://www.slideshare.net/anthonycrasto64/anthony-crasto-brevetoxin-synthesis

Brevetoxin (PbTx), or brevetoxins, are a suite of cyclic polyether compoundsproduced naturally by a species of dinoflagellate known asKarenia brevis.Brevetoxins are neurotoxins that bind to voltage-gated sodium channels in nervecells, leading to disruption of normal neurological processes and causing theillness clinically described as neurotoxic shellfish poisoning (NSP).Although brevetoxins are most well-studied in K. brevis, they are also found inother species of Karenia and at least one large fish kill has been traced tobrevetoxins in Chattonella

DR A.M. CRASTO



New developments on the cheminformatics open workflow environment CDK-Taverna

Andreas Truszkowski, Kalai Vanii Jayaseelan, Stefan Neumann, Egon L Willighagen, Achim Zielesny, Christoph SteinbeckJournal of Cheminformatics 2011, 3:54 (13 December 2011)

read at-- http://www.jcheminf.com/content/3/1/54/abstract

Bradshaw, Ben; Bonjoch, Josep:
The Wieland-Miescher Ketone: A Journey from Organocatalysis to Natural Product Synthesis 

Synlett 2012(3): 337-356  
DOI: 10.1055/s-0031-1290107

https://sites.google.com/site/rdforgmvp/  is the link to my site

https://sites.google.com/site/anthonycrastomolecules/  IS THE LINK

CLICK HERE TO ACCESSS

Anthony Crasto Patent Related Site

IS THE LINK TO MY PATENT RELATED INFORMATION

Carbon nanotubes (CNTs) have attracted considerable interest due to their unique structure and remarkable properties. Racemic drugs normally contain only one enantiomer that is active, and to get enantiomerically pure drugs to the market is always an urgent task. As promising reagents, chiral selector modified CNTs have been successfully used to separate enantiomers.

Jingang Yu and colleagues, Central South University, China, proposed a novel method to functionalize multi-walled carbon nanotubes (MWCNTs) with hydroxypropyl-β-cyclodextrin (HP-β-CD). These modified multi-walled nanotube samples were fully characterized.

MWCNT-HP-β-CD was used as thin-layer chromatography stationary phase additive to separate clenbuterol enantiomers with satisfactory results. The presence of CNTs permits a higher recognition of enantiomers, so chiral selector modified CNTs have a promising application in resolution of chiral molecules.

Preparation of Hydroxypropyl-β-cyclodextrin Cross-linked Multi-walled Carbon Nanotubes and Their Application in Enantioseparation of Clenbuterol
J. Yu, D. Huang, K. Huang, Y. Hong,
Chinese J. Chem. 2011, 29(5), 893—897.
DOI: 10.1002/cjoc.201190185

Chiral Separation by a Pseudo Membrane in a Triple-Laminar Flow with a Microfluidic Contactor
T.-H. Yoon, L.-Y. Hong, D.-P. Kim,
Chem. Asian J. 2011.
DOI: 10.1002/asia.201000798

The pharmacological activity of ibuprofen, a common painkiller and anti-inflammatory drug, arises predominantly from its (S)-form. Separation of the (R)- and (S)-forms is difficult as they differ only in optical polarity.

The continuous and simultaneous reaction/separation of ibuprofen racemate has been reported by Dong-Pyo Kim and co-workers, Chungnam National University, South Korea. They use an inorganic polymer-chip device with triple-laminar flow. A feed phase withCandida rugosa lipase was used to facilitate esterification of (S)-ibuprofen due to its selective chiral recoginition and resolution. The (S)-ibuprofen ester was then transported through an ionic liquid which acted as a pseudo-membrane. Finally, conversion into (S)-ibuprofen was achieved by H₂SO₄ acid hydrolysis in a receiving stream.

The separated ibuprofen revealed very high chiral purity, with 99.9 % enantiomeric excess throughout the process conditions

WELCOME TO MY SITE ON JIMDO

These sites are on varied topics of organic chemistry

click belowto get to my collection of sites 

 https://sites.google.com/site/anthonycrastoorganicchemistry

/sites---my-own-on-the-net

THANKS AND REGARD'S
DR ANTHONY MELVIN CRASTO Ph.D