sample thesis title with a concise and accurate description

More documents

Recommendations

Info

Dedication To my parents George and Martha, for all the car rides and sandwiches. It’s Friday. xxviii
Chapter 1: Marine Natural Products From Benchtop to Bedside 1.1 Nature as a Source of Medicine Mankind’s ability to harness nature as a source of medicine was a key step in the evolutionary success of our species. In the early stages of human history, plants were the main source of medicine. Phyta of different varieties were used for many purposes including seduction, probing the boundaries of consciousness, pain relief, and even suicide. 1,2,3,4 The 20 th century brought about a new era of scientific enlightenment, allowing us to probe the structure of these once esoteric biologically active molecules. No longer would myth and folklore surround plants such as mint, peyote, willow, and hemlock, instead the active components could now be isolated and identified (Figure 1.1). Furthermore, new chemical entities could be classified as terpenes, 5 alkaloids, 6 polyketides, 7 and nonribosomal peptides 8 based on their common structural motifs and putative biogenetic origins. Figure 1.1 Bioactive compounds of plants commonly used throughout human history. With the commercialization of SCUBA in the 1950’s, the shallow marine environment could be routinely explored. This catalyzed a renaissance in the field of natural products. It was realized that if bioactive compounds could be discovered from terrestrial sources, then the marine environment should provide a plethora of novel compounds as well. 1
Page 1 and 2: FUNCTION ORIENTED SYNTHESIS OF BIOA
Page 3 and 4: The fifth chapter describes synthet
Page 5 and 6: iological data and “click” chem
Page 7 and 8: 2.6 Synthesis of a Benzophenone Pho
Page 9 and 10: List of Tables Table 1.1 The proper
Page 11 and 12: Figure 2.12 CLogP values of 2.18 an
Page 13 and 14: Figure 2.41 1 H and 13 C NMR spectr
Page 17 and 18: Figure 4.6 AR competitor in vitro a
Page 21 and 22: Scheme 3.5 Synthesis of (R)-niphate
Page 23 and 24: List of Symbols and Abbreviations
Page 25 and 26: Lys - lysine m - multiplet M - mola
Page 27: Acknowledgements What a trip. First
Page 31 and 32: Table 1.1 The properties of natural
Page 33 and 34: deprotonates the secondary alcohol
Page 35 and 36: Figure 1.4 Marine natural product i
Page 37 and 38: sceptrin 28 (1.20), and (-)-agelife
Page 39 and 40: polyketide (+)-spongistatin 1 (1.27
Page 41 and 42: allowing for construction of simpli
Page 43 and 44: potency, and the synthetic efforts
Page 45 and 46: 4,5-P2, or PIP2). This generates an
Page 47 and 48: Figure 2.3 Pelorol (2.1) analogue 2
Page 49 and 50: 2.3 Synthesis of SHIP1 Activators U
Page 51 and 52: intramolecular attack by a nucleoph
Page 53 and 54: Scheme 2.4 Elimination side product
Page 55 and 56: As this issue of water solubility i
Page 57 and 58: Scheme 2.5 Inspiration for biomimet
Page 59 and 60: Scheme 2.7 Synthesis of amine analo
Page 61 and 62: Figure 2.13 ORTEP diagram of Mosher
Page 63 and 64: Reductive amination of oxime 2.41 g
Page 65 and 66: While primary amines 2.20 and 2.42
Page 67 and 68: interacts with SHIP1 and if there i
Page 69 and 70: Figure 2.18 STDD NMR sample prepara
Page 71 and 72: STDD effects are observed for proto
Page 73 and 74: Figure 2.22 Commonly used tags. The
Page 75 and 76: enzophenone fragment can come from
Page 77 and 78: with thionyl chloride gave acid chl
Page 79 and 80:
These two regioisomers could not be
Page 81 and 82:
This sample was stirred at room tem
Page 83 and 84:
minor �-amine epimers 2.34/2.43 s
Page 85 and 86:
2.8 Conclusion The activation of SH
Page 87 and 88:
mouse model. The compounds were eff
Page 89 and 90:
otations were measured with a JASCO
Page 91 and 92:
Preparation of 2.3/2.14: To a solut
Page 93 and 94:
Figure 2.28 1 H and 13 C NMR spectr
Page 95 and 96:
Preparation of (±)-2.26: To polyen
Page 97 and 98:
Preparation of 2.30: To epoxide 2.2
Page 99 and 100:
Preparation of 2.31: Alcohol 2.30 (
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Compound 2.20: 1 H NMR (600 MHz, CD
Page 111 and 112:
Page 113 and 114:
Preparation of 2.40: To 2.19 (20 mg
Page 115 and 116:
Preparation of 2.44: To 2.40 (10.3
Page 117 and 118:
Preparation of 2.45: To 2.44 (8.0 m
Page 119 and 120:
Preparation of 2.47: To sodium hydr
Page 121 and 122:
Preparation of 2.61: To acid chlori
Page 123 and 124:
Preparation of 2.53: To 2.61 (754 m
Page 125 and 126:
Figure 2.42 NOESY spectrum of 2.53
Page 127 and 128:
Dry Transfer system (Life Technolog
Page 129 and 130:
Chapter 3: Glycerol Ethers from the
Page 131 and 132:
Figure 3.2 Examples of antiandrogen
Page 133 and 134:
Figure 3.4 Small molecule antagonis
Page 135 and 136:
the benzyl protected glycerol ether
Page 137 and 138:
The synthesis of (R)-niphatenone B
Page 139 and 140:
and B (3.37) were isolated by Matsu
Page 141 and 142:
Scheme 3.8 Synthesis of a short cha
Page 143 and 144:
(3.31). This was accomplished by op
Page 145 and 146:
Acetonide 3.30 was hydrogenated in
Page 147 and 148:
of an active probe is the quinoline
Page 149 and 150:
conjugation is disrupted by the nuc
Page 151 and 152:
Figure 3.11 AR transcriptional acti
Page 153 and 154:
concentration of either (S) or (R)
Page 155 and 156:
Each natural product contains one s
Page 157 and 158:
Preparation of 3.16: Tetrahydrofura
Page 159 and 160:
Preparation of 3.17: To compound 3.
Page 161 and 162:
Preparation of 3.18: To alcohol 3.1
Page 163 and 164:
Preparation of 3.20: Phosphorane 3.
Page 165 and 166:
Page 167 and 168:
Page 169 and 170:
Preparation of 3.27: NaH (330 mg, 8
Page 171 and 172:
Page 173 and 174:
Preparation of 3.29: To Dess-Martin
Page 175 and 176:
Preparation of 3.30: To phosphonate
Page 177 and 178:
Preparation of 3.31: To acetonide 3
Page 179 and 180:
Preparation of 3.35: Procedures ide
Page 181 and 182:
Preparation of 3.34: To bromohydrin
Page 183 and 184:
Preparation of 3.25: To bromide 3.3
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Preparation of 3.41: To ketone 3.40
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Preparation of 3.48: Sodium hydride
Page 201 and 202:
Page 203 and 204:
Preparation of 3.50: To Dess-Martin
Page 205 and 206:
Page 207 and 208:
Page 209 and 210:
Page 211 and 212:
Page 213 and 214:
Preparation of 3.57: To bromine 3.2
Page 215 and 216:
Preparation of 3.58:� To 3.57 (2.
Page 217 and 218:
Preparation of 3.59:� To alcohol
Page 219 and 220:
Page 221 and 222:
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
AR Transcriptional Activity Assay:
Page 231 and 232:
Chapter 4: Synthetic Efforts Toward
Page 233 and 234:
Scheme 4.1 Semisynthesis of 4.1 ana
Page 235 and 236:
This synthetic route was devised wi
Page 237 and 238:
Scheme 4.5 Synthesis of regioisomer
Page 239 and 240:
Figure 4.4 Favored and disfavored r
Page 241 and 242:
An alternative strategy using 3-fur
Page 243 and 244:
Scheme 4.10 Mono-thiolated analogue
Page 245 and 246:
4.4 Biological Results The semisynt
Page 247 and 248:
Table 4.1 EC50 values for tested co
Page 249 and 250:
The focus of this chapter is dedica
Page 251 and 252:
Preparation of 4.16: To a solution
Page 253 and 254:
Page 255 and 256:
Page 257 and 258:
Preparation of 4.20: To (-)-DIPT (0
Page 259 and 260:
Page 261 and 262:
Preparation of 4.22: To bromide 4.1
Page 263 and 264:
Preparation of 4.23: To sulfone 4.2
Page 265 and 266:
Page 267 and 268:
Preparation of 4.40: To furan 4.12
Page 269 and 270:
Page 271 and 272:
Page 273 and 274:
Page 275 and 276:
Page 277 and 278:
Chapter 5: Synthetic Efforts Toward
Page 279 and 280:
Shortly afterwards, additional pept
Page 281 and 282:
the nM range in a cathepsin K enzym
Page 283 and 284:
Scheme 5.2 Synthesis toward lichost
Page 285 and 286:
primary alcohol and oxidizing it ba
Page 287 and 288:
was attempted in order to shorten f
Page 289 and 290:
Scheme 5.6 Alternative route to lic
Page 291 and 292:
ligand complex was analyzed by a be
Page 293 and 294:
Preparation of 5.12: To Fmoc-L-vali
Page 295 and 296:
Preparation of 5.13: To 5.12 (7.0 g
Page 297 and 298:
Preparation of 5.15: To O-benzyl-Bo
Page 299 and 300:
Page 301 and 302:
Preparation of 5.18: Mono Boc prote
Page 303 and 304:
Figure 5.9 1 H and 13 C NMR spectra
Page 305 and 306:
127.5, 127.4, 72.2, 70.6, 63.1, 57.
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Page 313 and 314:
Preparation of 5.32: To Fmoc-L-seri
Page 315 and 316:
Preparation of 5.33: 5.32 (591.3 mg
Page 317 and 318:
Preparation of 5.35: To the Fmoc pr
Page 319 and 320:
Preparation of 5.36: Compound 5.35
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
Preparation of 5.39: To Boc protect
Page 327 and 328:
Page 329 and 330:
Chapter 6: Conclusion 6.1 Biologica
Page 331 and 332:
either niphatenone A (3.8) and/or B
Page 333 and 334:
Scheme 6.2 Lithiation strategy to c
Page 335 and 336:
Scheme 6.4 Alternative synthesis of
Page 337 and 338:
References (1) McGovern, P. E.; Mir
Page 339 and 340:
(31) Seiple, I. B.; Su, S.; Young,
Page 341 and 342:
(55) Woodward, R.; Bloch, K. J. Am.
Page 343 and 344:
(86) Parra-Delgado, H.; Compadre, C
Page 345 and 346:
(112) Bi, X.; Schmitz, A.; Hayallah
Page 347 and 348:
(140) Sadar, M. D.; Williams, D. E.
Page 349 and 350:
(167) Zoretic, P.; Wang, M.; Zhang,
Page 351 and 352:
(199) Mohamed, M. M.; Sloane, B. F.
Page 353 and 354:
(224) Shimokawa, J.; Ishiwata, T.;
Page 355 and 356:
Crystal Data: Empirical Formula C23
Page 357 and 358:
Structure Solution and Refinement:
Page 359 and 360:
Crystal Data: Empirical Formula C33
Page 361 and 362:
Page 363 and 364:
non-hydrogen atoms were refined ani
Page 365:
show all

sample thesis title with a concise and accurate description

Create successful ePaper yourself

Delete template?

Save as template?