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| | <title>Aomy/Project</title> | | <title>Aomy/Project</title> |
| | | | |
| − | <style type="text/css"> | + | <link ref="stylesheet" href="https://2015.igem.org/Template:Amoy/css/Project/BackgroundCss?action=raw&ctype=text/css" type="text/css" /> |
| − | body
| + | |
| − | {
| + | |
| − | background-color: #fff;
| + | |
| − | }
| + | |
| − | | + | |
| − | #content
| + | |
| − | {
| + | |
| − | padding: 0; border: 0; width: 100%;
| + | |
| − | }
| + | |
| − | | + | |
| − | .firstHeading
| + | |
| − | {
| + | |
| − | visibility: hidden;
| + | |
| − | }
| + | |
| − | | + | |
| − | #menu
| + | |
| − | {
| + | |
| − | width: 100%;
| + | |
| − | height: 200px;
| + | |
| − | overflow: hidden;
| + | |
| − | margin-top: -50px;
| + | |
| − | position: absolute;
| + | |
| − | }
| + | |
| − | | + | |
| − | #logo
| + | |
| − | {
| + | |
| − | position: absolute;
| + | |
| − | width: 115px;
| + | |
| − | height: 70px;
| + | |
| − | margin-top: -20px;
| + | |
| − | margin-left: 20px;
| + | |
| − | z-index:999;
| + | |
| − | }
| + | |
| − | | + | |
| − | | + | |
| − | | + | |
| − | html,body,div,dl,dt,dd,ul,ol,li,h1,h2,h3,h4,h5,h6,pre,code,form,fieldset,legend,input,textarea,p,blockquote,th,td
| + | |
| − | {
| + | |
| − | font-family: Helvetica, Tahoma, Arial, "Hiragino Sans GB", "Hiragino Sans GB W3", "Microsoft YaHei", STXihei, STHeiti, Heiti, SimSun, sans-serif;
| + | |
| − | font-size: 12px;
| + | |
| − | }
| + | |
| − | #cssmenu,
| + | |
| − | #cssmenu ul,
| + | |
| − | #cssmenu ul li,
| + | |
| − | #cssmenu ul li a,
| + | |
| − | #cssmenu #menu-button {
| + | |
| − | margin: 0;
| + | |
| − | padding: 0;
| + | |
| − | border: 0;
| + | |
| − | list-style: none;
| + | |
| − | line-height: 1;
| + | |
| − | display: block;
| + | |
| − | position: relative;
| + | |
| − | -webkit-box-sizing: border-box;
| + | |
| − | -moz-box-sizing: border-box;
| + | |
| − | box-sizing: border-box;
| + | |
| − | }
| + | |
| − | #cssmenu:after,
| + | |
| − | #cssmenu > ul:after {
| + | |
| − | content: ".";
| + | |
| − | display: block;
| + | |
| − | clear: both;
| + | |
| − | visibility: hidden;
| + | |
| − | line-height: 0;
| + | |
| − | height: 0;
| + | |
| − | }
| + | |
| − | #cssmenu #menu-button {
| + | |
| − | display: none;
| + | |
| − | }
| + | |
| − | #cssmenu {
| + | |
| − | width: auto;
| + | |
| − | font-family: 'Open Sans', sans-serif;
| + | |
| − | line-height: 1;
| + | |
| − | font-weight: bold;
| + | |
| − | | + | |
| − | }
| + | |
| − | #menu-line {
| + | |
| − | position: absolute;
| + | |
| − | top: 0;
| + | |
| − | left: 0;
| + | |
| − | height: 3px;
| + | |
| − | background: #009ae1;
| + | |
| − | -webkit-transition: all 0.25s ease-out;
| + | |
| − | -moz-transition: all 0.25s ease-out;
| + | |
| − | -ms-transition: all 0.25s ease-out;
| + | |
| − | -o-transition: all 0.25s ease-out;
| + | |
| − | transition: all 0.25s ease-out;
| + | |
| − | }
| + | |
| − | #cssmenu > ul > li {
| + | |
| − | float: left;
| + | |
| − | }
| + | |
| − | #cssmenu.align-center > ul {
| + | |
| − | font-size: 0;
| + | |
| − | text-align: center;
| + | |
| − | }
| + | |
| − | #cssmenu.align-center > ul > li {
| + | |
| − | display: inline-block;
| + | |
| − | float: none;
| + | |
| − | }
| + | |
| − | #cssmenu.align-center ul ul {
| + | |
| − | text-align: left;
| + | |
| − | }
| + | |
| − | #cssmenu.align-right > ul > li {
| + | |
| − | float: right;
| + | |
| − | }
| + | |
| − | #cssmenu.align-right ul ul {
| + | |
| − | text-align: right;
| + | |
| − | }
| + | |
| − | #cssmenu > ul > li > a {
| + | |
| − | margin-right: 40px;
| + | |
| − | padding-top: 20px;
| + | |
| − | font-size: 12px;
| + | |
| − | text-decoration: none;
| + | |
| − | text-transform: uppercase;
| + | |
| − | color: #fff;
| + | |
| − | -webkit-transition: color .2s ease;
| + | |
| − | -moz-transition: color .2s ease;
| + | |
| − | -ms-transition: color .2s ease;
| + | |
| − | -o-transition: color .2s ease;
| + | |
| − | transition: color .2s ease;
| + | |
| − | }
| + | |
| − | | + | |
| − | #cssmenu > ul > li:hover > a,
| + | |
| − | #cssmenu > ul > li.active > a
| + | |
| − | {
| + | |
| − | border-bottom: 1.5px solid #fff;
| + | |
| − | padding-bottom: 5px;
| + | |
| − | | + | |
| − | }
| + | |
| − | | + | |
| − | #cssmenu > ul > li.has-sub > a {
| + | |
| − | margin-right: 40px;
| + | |
| − | }
| + | |
| − | #cssmenu > ul > li.has-sub > a::after {
| + | |
| − | position: absolute;
| + | |
| − | top: 21px;
| + | |
| − | right: -18px;
| + | |
| − | width: 4px;
| + | |
| − | height: 4px;
| + | |
| − | border-bottom: 1px solid #fff;
| + | |
| − | border-right: 1px solid #fff;
| + | |
| − | content: "";
| + | |
| − | -webkit-transform: rotate(45deg);
| + | |
| − | -moz-transform: rotate(45deg);
| + | |
| − | -ms-transform: rotate(45deg);
| + | |
| − | -o-transform: rotate(45deg);
| + | |
| − | transform: rotate(45deg);
| + | |
| − | -webkit-transition: border-color 0.2s ease;
| + | |
| − | -moz-transition: border-color 0.2s ease;
| + | |
| − | -ms-transition: border-color 0.2s ease;
| + | |
| − | -o-transition: border-color 0.2s ease;
| + | |
| − | transition: border-color 0.2s ease;
| + | |
| − | }
| + | |
| − | #cssmenu > ul > li.has-sub:hover > a::after {
| + | |
| − | }
| + | |
| − | #cssmenu ul ul {
| + | |
| − | position: absolute;
| + | |
| − | left: -9999px;
| + | |
| − | }
| + | |
| − | #cssmenu li:hover > ul {
| + | |
| − | left: auto;
| + | |
| − | }
| + | |
| − | #cssmenu.align-right li:hover > ul {
| + | |
| − | right: 0;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul ul {
| + | |
| − | margin-left: 100%;
| + | |
| − | top: 0;
| + | |
| − | }
| + | |
| − | #cssmenu.align-right ul ul ul {
| + | |
| − | margin-left: 0;
| + | |
| − | margin-right: 100%;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul li {
| + | |
| − | height: 0;
| + | |
| − | -webkit-transition: height .2s ease;
| + | |
| − | -moz-transition: height .2s ease;
| + | |
| − | -ms-transition: height .2s ease;
| + | |
| − | -o-transition: height .2s ease;
| + | |
| − | transition: height .2s ease;
| + | |
| − | }
| + | |
| − | #cssmenu ul li:hover > ul > li {
| + | |
| − | height: 32px;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul li a {
| + | |
| − | padding: 10px 20px;
| + | |
| − | width: 160px;
| + | |
| − | font-size: 12px;
| + | |
| − | background: #333333;
| + | |
| − | text-decoration: none;
| + | |
| − | color: #dddddd;
| + | |
| − | -webkit-transition: color .2s ease;
| + | |
| − | -moz-transition: color .2s ease;
| + | |
| − | -ms-transition: color .2s ease;
| + | |
| − | -o-transition: color .2s ease;
| + | |
| − | transition: color .2s ease;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul li:hover > a,
| + | |
| − | #cssmenu ul ul li a:hover {
| + | |
| − | color: #ffffff;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul li.has-sub > a::after {
| + | |
| − | position: absolute;
| + | |
| − | top: 13px;
| + | |
| − | right: 10px;
| + | |
| − | width: 4px;
| + | |
| − | height: 4px;
| + | |
| − | border-bottom: 1px solid #dddddd;
| + | |
| − | border-right: 1px solid #dddddd;
| + | |
| − | content: "";
| + | |
| − | -webkit-transform: rotate(-45deg);
| + | |
| − | -moz-transform: rotate(-45deg);
| + | |
| − | -ms-transform: rotate(-45deg);
| + | |
| − | -o-transform: rotate(-45deg);
| + | |
| − | transform: rotate(-45deg);
| + | |
| − | -webkit-transition: border-color 0.2s ease;
| + | |
| − | -moz-transition: border-color 0.2s ease;
| + | |
| − | -ms-transition: border-color 0.2s ease;
| + | |
| − | -o-transition: border-color 0.2s ease;
| + | |
| − | transition: border-color 0.2s ease;
| + | |
| − | }
| + | |
| − | #cssmenu.align-right ul ul li.has-sub > a::after {
| + | |
| − | right: auto;
| + | |
| − | left: 10px;
| + | |
| − | border-bottom: 0;
| + | |
| − | border-right: 0;
| + | |
| − | border-top: 1px solid #dddddd;
| + | |
| − | border-left: 1px solid #dddddd;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul li.has-sub:hover > a::after {
| + | |
| − | border-color: #ffffff;
| + | |
| − | }
| + | |
| − | @media all and (max-width: 768px), only screen and (-webkit-min-device-pixel-ratio: 2) and (max-width: 1024px), only screen and (min--moz-device-pixel-ratio: 2) and (max-width: 1024px), only screen and (-o-min-device-pixel-ratio: 2/1) and (max-width: 1024px), only screen and (min-device-pixel-ratio: 2) and (max-width: 1024px), only screen and (min-resolution: 192dpi) and (max-width: 1024px), only screen and (min-resolution: 2dppx) and (max-width: 1024px) {
| + | |
| − | #cssmenu {
| + | |
| − | width: 100%;
| + | |
| − | }
| + | |
| − | #cssmenu ul {
| + | |
| − | width: 100%;
| + | |
| − | display: none;
| + | |
| − | }
| + | |
| − | #cssmenu.align-center > ul,
| + | |
| − | #cssmenu.align-right ul ul {
| + | |
| − | text-align: left;
| + | |
| − | }
| + | |
| − | #cssmenu ul li,
| + | |
| − | #cssmenu ul ul li,
| + | |
| − | #cssmenu ul li:hover > ul > li {
| + | |
| − | width: 100%;
| + | |
| − | height: auto;
| + | |
| − | border-top: 1px solid rgba(120, 120, 120, 0.15);
| + | |
| − | }
| + | |
| − | #cssmenu ul li a,
| + | |
| − | #cssmenu ul ul li a {
| + | |
| − | width: 100%;
| + | |
| − | }
| + | |
| − | #cssmenu > ul > li,
| + | |
| − | #cssmenu.align-center > ul > li,
| + | |
| − | #cssmenu.align-right > ul > li {
| + | |
| − | float: none;
| + | |
| − | display: block;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul li a {
| + | |
| − | padding: 20px 20px 20px 30px;
| + | |
| − | font-size: 12px;
| + | |
| − | color: #000000;
| + | |
| − | background: none;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul li:hover > a,
| + | |
| − | #cssmenu ul ul li a:hover {
| + | |
| − | color: #000000;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul ul li a {
| + | |
| − | padding-left: 40px;
| + | |
| − | }
| + | |
| − | #cssmenu ul ul,
| + | |
| − | #cssmenu ul ul ul {
| + | |
| − | position: relative;
| + | |
| − | left: 0;
| + | |
| − | right: auto;
| + | |
| − | width: 100%;
| + | |
| − | margin: 0;
| + | |
| − | }
| + | |
| − | #cssmenu > ul > li.has-sub > a::after,
| + | |
| − | #cssmenu ul ul li.has-sub > a::after {
| + | |
| − | display: none;
| + | |
| − | }
| + | |
| − | #menu-line {
| + | |
| − | display: none;
| + | |
| − | }
| + | |
| − | #cssmenu #menu-button {
| + | |
| − | display: block;
| + | |
| − | padding: 20px;
| + | |
| − | color: #000000;
| + | |
| − | cursor: pointer;
| + | |
| − | font-size: 12px;
| + | |
| − | text-transform: uppercase;
| + | |
| − | }
| + | |
| − | #cssmenu #menu-button::after {
| + | |
| − | content: '';
| + | |
| − | position: absolute;
| + | |
| − | top: 20px;
| + | |
| − | right: 20px;
| + | |
| − | display: block;
| + | |
| − | width: 15px;
| + | |
| − | height: 2px;
| + | |
| − | background: #000000;
| + | |
| − | }
| + | |
| − | #cssmenu #menu-button::before {
| + | |
| − | content: '';
| + | |
| − | position: absolute;
| + | |
| − | top: 25px;
| + | |
| − | right: 20px;
| + | |
| − | display: block;
| + | |
| − | width: 15px;
| + | |
| − | height: 3px;
| + | |
| − | border-top: 2px solid #000000;
| + | |
| − | border-bottom: 2px solid #000000;
| + | |
| − | }
| + | |
| − | #cssmenu .submenu-button {
| + | |
| − | position: absolute;
| + | |
| − | z-index: 10;
| + | |
| − | right: 0;
| + | |
| − | top: 0;
| + | |
| − | display: block;
| + | |
| − | border-left: 1px solid rgba(120, 120, 120, 0.15);
| + | |
| − | height: 52px;
| + | |
| − | width: 52px;
| + | |
| − | cursor: pointer;
| + | |
| − | }
| + | |
| − | #cssmenu .submenu-button::after {
| + | |
| − | content: '';
| + | |
| − | position: absolute;
| + | |
| − | top: 21px;
| + | |
| − | left: 26px;
| + | |
| − | display: block;
| + | |
| − | width: 1px;
| + | |
| − | height: 11px;
| + | |
| − | background: #000000;
| + | |
| − | z-index: 99;
| + | |
| − | }
| + | |
| − | #cssmenu .submenu-button::before {
| + | |
| − | content: '';
| + | |
| − | position: absolute;
| + | |
| − | left: 21px;
| + | |
| − | top: 26px;
| + | |
| − | display: block;
| + | |
| − | width: 11px;
| + | |
| − | height: 1px;
| + | |
| − | background: #000000;
| + | |
| − | z-index: 99;
| + | |
| − | }
| + | |
| − | #cssmenu .submenu-button.submenu-opened:after {
| + | |
| − | display: none;
| + | |
| − | }
| + | |
| − | }
| + | |
| − | | + | |
| − | #project_abstract{
| + | |
| − | padding-right: 20px;
| + | |
| − | padding-left: 20px;
| + | |
| − | }
| + | |
| − | | + | |
| − | #cssmenu
| + | |
| − | {
| + | |
| − | position: absolute;
| + | |
| − | right: 20px;
| + | |
| − | margin-top: -20px;
| + | |
| − | }
| + | |
| − | | + | |
| − | #triangle
| + | |
| − | {
| + | |
| − | margin-left: 48%;
| + | |
| − | position: absolute;
| + | |
| − | margin-top: 150px;
| + | |
| − | z-index: -10;
| + | |
| − | }
| + | |
| − | | + | |
| − | #triangle_pic
| + | |
| − | {
| + | |
| − | width: 20px;
| + | |
| − | height: 10px;
| + | |
| − | }
| + | |
| − | | + | |
| − | #main_content
| + | |
| − | {
| + | |
| − | position: absolute;
| + | |
| − | margin-top: 170px;
| + | |
| − | width: 100%;
| + | |
| − | }
| + | |
| − | | + | |
| − | #s_menu
| + | |
| − | {
| + | |
| − | position: fixed;
| + | |
| − | width: 13%;
| + | |
| − | left: 5%;
| + | |
| − | margin-top: 50px;
| + | |
| − | }
| + | |
| − | | + | |
| − | #s_menu h4
| + | |
| − | {
| + | |
| − | font-size: 20px;
| + | |
| − | margin-left: 18px;
| + | |
| − | border-bottom: 2px solid #147abc;
| + | |
| − | padding-bottom: 10px;
| + | |
| − | color: #147abc;
| + | |
| − | }
| + | |
| − | | + | |
| − | .ul_menu
| + | |
| − | {
| + | |
| − | margin-top: 15px;
| + | |
| − | list-style: none;
| + | |
| − | }
| + | |
| − | | + | |
| − | .ul_menu li a
| + | |
| − | {
| + | |
| − | display:block;
| + | |
| − | font-size: 15px;
| + | |
| − | margin-top: 10px;
| + | |
| − | text-decoration: none;
| + | |
| − | color: #778899;
| + | |
| − | }
| + | |
| − | | + | |
| − | .ul_menu li:hover
| + | |
| − | {
| + | |
| − | color: #147abc;
| + | |
| − | margin-left: 10px;
| + | |
| − | }
| + | |
| − | | + | |
| − | #title
| + | |
| − | {
| + | |
| − | position: absolute;
| + | |
| − | width: 75%;
| + | |
| − | right: 2%;
| + | |
| − | }
| + | |
| − | | + | |
| − | #title_p
| + | |
| − | {
| + | |
| − | color: #147abc;
| + | |
| − | font-size: 40px;
| + | |
| − | text-align: center;
| + | |
| − | }
| + | |
| − | | + | |
| − | .main_p
| + | |
| − | {
| + | |
| − | font-size: 15px;
| + | |
| − | padding-left: 80px;
| + | |
| − | padding-right: 80px;
| + | |
| − | }
| + | |
| − | | + | |
| − | .main_h1
| + | |
| − | {
| + | |
| − | margin-left: 80px;
| + | |
| − | font-size: 20px;
| + | |
| − | margin-top: 20px;
| + | |
| − | }
| + | |
| − | | + | |
| − | .main_img
| + | |
| − | {
| + | |
| − | margin-left: 80px;
| + | |
| − | margin-top: 15px;
| + | |
| − | margin-bottom: 15px;
| + | |
| − | }
| + | |
| − | | + | |
| − | </style>
| + | |
| | | | |
| | </head> | | </head> |
BackgroundThe Application of L-tert-leucine
L-tert-leucine is an important and attractive chiral building block. Owing to its bulky and hydrophobic tert-butyl side chain which would provide particularly great steric hindrance in the process of reaction, this unnatural amino acid is widely used as chiral auxiliaries and catalysts in asymmetric synthesis in developing chiral pharmaceutically active chemicals.
1.1. Asymmetric synthesis by L-tert-leucine and its derivatives
When L-tert-leucine or its derivatives were employed in asymmetric reactions, the results always showed high enantioselectivities. For example, the following reaction is a reported Michael additions of Grignard reagents to a,b-unsaturated aldimines derived from L-tert-leucine (Figure 1). After hydrolysis and hydrogenation, the finalist product shows high enantiomerical purity. Owing to the bulky tert-butyl side chain of compound 1, the side of stronger steric hindrance was locked. Grignard reagents could only attack compound 1 from the special side so that the product shows high enantiomerical purity.
1.2. Pharmaceutical applications of L-tert-leucine
L-tert-leucine can applied in various Pharmaceutical field. L-tert-leucine was introducted into new and more efficient protease inhibitors of many viral diseases, such as HIV, IL-l-induced cartilage degradation and so on.
As we can see, AIDS is an awful disease which disturbed humans for many years. Investigations show that HIV-protease is an aspartic acid protease which is necessary for viral replication. So inhibition of this protease makes HIV non-infectious. The most favorable HIV-protease inhibitors structure are phenylnorstatine [(2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid, Figure 2] and its derivatives.
In order to optimized protease inhibitors, numerous protected, deprotected and derivatized L-tert-leucines are used to modify phenylnorstatine. Modified compounds could be nice protease inhibitors with considerable antiviral activity.
For the treatment of IL-l-induced cartilage degradation in tissue culture , L-tert-leucine plays an important role. Thirty years ago, Roche company discoved an N-substituted Tle-N-methylamide (Ro 31-9790, Figure 3) to be an potent collagenase inhibitor which could prevent IL-l-induced cartilage degradation.
L-tert-leucine is essential in many fields so that the large-scale production is indispensible.
Reference
1. Takayuki Shioiri, Kunisuke Izawa, and Toshiro Konoike. Pharmaceutical Process Chemistry. WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 2011. 184-205
2. Andreas S. Bommarius, Michael Schwarm, Klaus Stingl, Matthias Kottenhahn, Klaus Huthmacher and Karlheinz Drauz. Synthesis and Use of Enantiomerically Pure tert-Leucine.Tetrahedron: Asymmetry. 1995, 6, 2851-2888
3. P. Ettmayer, M. Hübner, A. Billich, B. Rosenwirth, H. Gstach, Bioorg. Med.Chem. Lett. 1994, 4, 2851-2856
4. D. J. Kempf, L. M. Codacovi, D. W. Norbeck, J. J. Plattner, H. Sham, S. J. Wittenberger, C. Zhao (Abbott), Patent Appl. EP 486948, 1992
5. P. A. Brown, W. H. Johnson, G. Lawton (Hoffmann-La Roche), EP Appl. 0497 192, 1992
