The historic center is surrounded by 11 kilometers of City walls. These were complemented by fortifications along the coast, which these became Cartagena an impregnable city. The walls were designed in order to protect the city from the continuous pirate attacks suffered. The city walls were made in several stages. The first construction was made in 1586

Rodrigo de Bastidas traveled to the Pearl Coast and the Gulf of Uraba in 1500–01. On 14 February 1504, Ferdinand V contracted Juan de la Cosa’s voyage to Uraba. However, Juan de la Cosa died in 1510 along with 300 of Alonso de Ojeda’s men, after an armed confrontation with indigenous people, and before Juan de la Cosa could get possession of the Gulf of Urabá area. Similar contracts were signed in 1508 with Diego de Nicuesa for the settlement of Veragua and with Alonso de Ojeda for the settlement of Uraba, “where gold had already been obtained on earlier voyages,” according to Floyd.

After the failed effort to find Antigua del Darién in 1506 by Alonso de Ojeda and the subsequent unsuccessful founding of San Sebastián de Urabá in 1517 by Diego de Nicuesa, the southern Caribbean coast became unattractive to colonizers. They preferred the better known Hispaniola and Cuba.

Although the royal control point for trade, the Casa de Contratación gave permission to Rodrigo de Bastidas (1460–1527) to again conduct an expedition as adelantado to this area, Bastidas explored the coast and sighted the Magdalena River Delta in his first journey from Guajira to the south in 1527, a trip that ended in the Gulf of Urabá, the location of the failed first settlements. De Nicuesa and De Ojeda noted the existence of a big bay on the way from Santo Domingo to Urabá and the Panama isthmus, and that encouraged Bastidas to investigate.

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